Yuka Morikawa, PhD
Texas Heart Institute Positions
- Assistant Research Investigator, Cardiomyocyte Renewal Laboratory
Publications
4862227
SS2CP8WX
1
alternatives-to-animal-experimentation
10
date
desc
Morikawa
2017
https://www.texasheart.org/wp-content/plugins/zotpress/
%7B%22status%22%3A%22success%22%2C%22updateneeded%22%3Afalse%2C%22instance%22%3Afalse%2C%22meta%22%3A%7B%22request_last%22%3A0%2C%22request_next%22%3A0%2C%22used_cache%22%3Atrue%7D%2C%22data%22%3A%5B%7B%22key%22%3A%222IUR7VCL%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Hill%20et%20al.%22%2C%22parsedDate%22%3A%222022-06-22%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EHill%2C%20M.%20C.%2C%20Kadow%2C%20Z.%20A.%2C%20Long%2C%20H.%20et%20al.%20%282022%29.%20Integrated%20multi-omic%20characterization%20of%20congenital%20heart%20disease.%20%3Ci%3ENature%3C%5C%2Fi%3E.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41586-022-04989-3%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41586-022-04989-3%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Integrated%20multi-omic%20characterization%20of%20congenital%20heart%20disease%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%20C.%22%2C%22lastName%22%3A%22Hill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zachary%20A.%22%2C%22lastName%22%3A%22Kadow%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Hali%22%2C%22lastName%22%3A%22Long%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thomas%20J.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Emma%20J.%22%2C%22lastName%22%3A%22Birks%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kenneth%20S.%22%2C%22lastName%22%3A%22Campbell%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jeanne%22%2C%22lastName%22%3A%22Nerbonne%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kory%22%2C%22lastName%22%3A%22Lavine%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lalita%22%2C%22lastName%22%3A%22Wadhwa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jun%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Diwakar%22%2C%22lastName%22%3A%22Turaga%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Iki%22%2C%22lastName%22%3A%22Adachi%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22The%20heart%2C%20the%20first%20organ%20to%20develop%20in%20the%20embryo%2C%20undergoes%20complex%20morphogenesis%20that%20when%20defective%20results%20in%20congenital%20heart%20disease%20%28CHD%29.%20With%20current%20therapies%2C%20more%20than%2090%25%20of%20patients%20with%20CHD%20survive%20into%20adulthood%2C%20but%20many%20suffer%20premature%20death%20from%20heart%20failure%20and%20non-cardiac%20causes1.%20Here%2C%20to%20gain%20insight%20into%20this%20disease%20progression%2C%20we%20performed%20single-nucleus%20RNA%20sequencing%20on%20157%2C273%20nuclei%20from%20control%20hearts%20and%20hearts%20from%20patients%20with%20CHD%2C%20including%20those%20with%20hypoplastic%20left%20heart%20syndrome%20%28HLHS%29%20and%20tetralogy%20of%20Fallot%2C%20two%20common%20forms%20of%20cyanotic%20CHD%20lesions%2C%20as%20well%20as%20dilated%20and%20hypertrophic%20cardiomyopathies.%20We%20observed%20CHD-specific%20cell%20states%20in%20cardiomyocytes%2C%20which%20showed%20evidence%20of%20insulin%20resistance%20and%20increased%20expression%20of%20genes%20associated%20with%20FOXO%20signalling%20and%20CRIM1.%20Cardiac%20fibroblasts%20in%20HLHS%20were%20enriched%20in%20a%20low-Hippo%20and%20high-YAP%20cell%20state%20characteristic%20of%20activated%20cardiac%20fibroblasts.%20Imaging%20mass%20cytometry%20uncovered%20a%20spatially%20resolved%20perivascular%20microenvironment%20consistent%20with%20an%20immunodeficient%20state%20in%20CHD.%20Peripheral%20immune%20cell%20profiling%20suggested%20deficient%20monocytic%20immunity%20in%20CHD%2C%20in%20agreement%20with%20the%20predilection%20in%20CHD%20to%20infection%20and%20cancer2.%20Our%20comprehensive%20phenotyping%20of%20CHD%20provides%20a%20roadmap%20towards%20future%20personalized%20treatments%20for%20CHD.%22%2C%22date%22%3A%22June%2022%202022%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41586-022-04989-3%22%2C%22ISSN%22%3A%221476-4687%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22SS2CP8WX%22%2C%22AMEMBFXC%22%2C%222RCWVZ4F%22%5D%2C%22dateModified%22%3A%222023-03-07T21%3A49%3A47Z%22%7D%7D%2C%7B%22key%22%3A%223FAUHUDK%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Aharonov%20et%20al.%22%2C%22parsedDate%22%3A%222020-11%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EAharonov%2C%20A.%2C%20Shakked%2C%20A.%2C%20Umansky%2C%20K.%20B.%20et%20al.%20%282020%29.%20ERBB2%20drives%20YAP%20activation%20and%20EMT-like%20processes%20during%20cardiac%20regeneration.%20%3Ci%3ENat%20Cell%20Biol%3C%5C%2Fi%3E%20%3Ci%3E22%3C%5C%2Fi%3E%2C%201346%26%23x2013%3B1356.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41556-020-00588-4%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fs41556-020-00588-4%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22ERBB2%20drives%20YAP%20activation%20and%20EMT-like%20processes%20during%20cardiac%20regeneration%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alla%22%2C%22lastName%22%3A%22Aharonov%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Avraham%22%2C%22lastName%22%3A%22Shakked%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kfir%20Baruch%22%2C%22lastName%22%3A%22Umansky%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alon%22%2C%22lastName%22%3A%22Savidor%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexander%22%2C%22lastName%22%3A%22Genzelinakh%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22David%22%2C%22lastName%22%3A%22Kain%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Daria%22%2C%22lastName%22%3A%22Lendengolts%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Or-Yam%22%2C%22lastName%22%3A%22Revach%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jixin%22%2C%22lastName%22%3A%22Dong%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yishai%22%2C%22lastName%22%3A%22Levin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Benjamin%22%2C%22lastName%22%3A%22Geiger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eldad%22%2C%22lastName%22%3A%22Tzahor%22%7D%5D%2C%22abstractNote%22%3A%22Cardiomyocyte%20loss%20after%20injury%20results%20in%20adverse%20remodelling%20and%20fibrosis%2C%20inevitably%20leading%20to%20heart%20failure.%20The%20ERBB2-Neuregulin%20and%20Hippo-YAP%20signalling%20pathways%20are%20key%20mediators%20of%20heart%20regeneration%2C%20yet%20the%20crosstalk%20between%20them%20is%20unclear.%20We%20demonstrate%20that%20transient%20overexpression%20of%20activated%20ERBB2%20in%20cardiomyocytes%20%28OE%20CMs%29%20promotes%20cardiac%20regeneration%20in%20a%20heart%20failure%20model.%20OE%20CMs%20present%20an%20epithelial-mesenchymal%20transition%20%28EMT%29-like%20regenerative%20response%20manifested%20by%20cytoskeletal%20remodelling%2C%20junction%20dissolution%2C%20migration%20and%20extracellular%20matrix%20turnover.%20We%20identified%20YAP%20as%20a%20critical%20mediator%20of%20ERBB2%20signalling.%20In%20OE%20CMs%2C%20YAP%20interacts%20with%20nuclear-envelope%20and%20cytoskeletal%20components%2C%20reflecting%20an%20altered%20mechanical%20state%20elicited%20by%20ERBB2.%20We%20identified%20two%20YAP-activating%20phosphorylations%20on%20S352%20and%20S274%20in%20OE%20CMs%2C%20which%20peak%20during%20metaphase%2C%20that%20are%20ERK%20dependent%20and%20Hippo%20independent.%20Viral%20overexpression%20of%20YAP%20phospho-mutants%20dampened%20the%20proliferative%20competence%20of%20OE%20CMs.%20Together%2C%20we%20reveal%20a%20potent%20ERBB2-mediated%20YAP%20mechanotransduction%20signalling%2C%20involving%20EMT-like%20characteristics%2C%20resulting%20in%20robust%20heart%20regeneration.%22%2C%22date%22%3A%22Nov%202020%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fs41556-020-00588-4%22%2C%22ISSN%22%3A%221476-4679%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22SS2CP8WX%22%5D%2C%22dateModified%22%3A%222020-12-07T18%3A33%3A50Z%22%7D%7D%2C%7B%22key%22%3A%22MXGXWS47%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Monroe%20et%20al.%22%2C%22parsedDate%22%3A%222019-03-25%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EMonroe%2C%20T.%20O.%2C%20Hill%2C%20M.%20C.%2C%20%3Cstrong%3EMorikawa%3C%5C%2Fstrong%3E%2C%20Y.%20et%20al.%20%282019%29.%20YAP%20partially%20reprograms%20chromatin%20accessibility%20to%20directly%20induce%20adult%20cardiogenesis%20in%26%23xA0%3Bvivo.%20%3Ci%3EDev%20Cell%3C%5C%2Fi%3E%20%3Ci%3E48%3C%5C%2Fi%3E%2C%20765-779.e7.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.devcel.2019.01.017%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.devcel.2019.01.017%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22YAP%20partially%20reprograms%20chromatin%20accessibility%20to%20directly%20induce%20adult%20cardiogenesis%20in%5Cu00a0vivo%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Tanner%20O.%22%2C%22lastName%22%3A%22Monroe%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%20C.%22%2C%22lastName%22%3A%22Hill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20P.%22%2C%22lastName%22%3A%22Leach%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Todd%22%2C%22lastName%22%3A%22Heallen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shuyi%22%2C%22lastName%22%3A%22Cao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Peter%20H.%20L.%22%2C%22lastName%22%3A%22Krijger%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wouter%22%2C%22lastName%22%3A%22de%20Laat%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Xander%20H.%20T.%22%2C%22lastName%22%3A%22Wehrens%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22George%20G.%22%2C%22lastName%22%3A%22Rodney%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22Specialized%20adult%20somatic%20cells%2C%20such%20as%20cardiomyocytes%20%28CMs%29%2C%20are%20highly%20differentiated%20with%20poor%20renewal%20capacity%2C%20an%20integral%20reason%20underlying%20organ%20failure%20in%20disease%20and%20aging.%20Among%20the%20least%20renewable%20cells%20in%20the%20human%20body%2C%20CMs%20renew%20approximately%201%25%20annually.%20Consistent%20with%20poor%20CM%20turnover%2C%20heart%20failure%20is%20the%20leading%20cause%20of%20death.%20Here%2C%20we%20show%20that%20an%20active%20version%20of%20the%5Cu00a0Hippo%20pathway%20effector%20YAP%2C%20termed%20YAP5SA%2C%20partially%20reprograms%20adult%20mouse%20CMs%20to%20a%20more%20fetal%20and%20proliferative%20state.%20One%20week%20after%20induction%2C%2019%25%20of%20CMs%20that%20enter%20S-phase%20do%20so%20twice%2C%20CM%20number%20increases%20by%2040%25%2C%20and%20YAP5SA%20lineage%20CMs%20couple%20to%20pre-existing%20CMs.%20Genomic%20studies%20showed%20that%20YAP5SA%20increases%20chromatin%20accessibility%20and%20expression%20of%20fetal%20genes%2C%20partially%20reprogramming%20long-lived%20somatic%20cells%20in%5Cu00a0vivo%20to%20a%20primitive%2C%20fetal-like%2C%20and%20proliferative%20state.%22%2C%22date%22%3A%22Mar%2025%2C%202019%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.devcel.2019.01.017%22%2C%22ISSN%22%3A%221878-1551%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22QH7R47P9%22%2C%22SS2CP8WX%22%5D%2C%22dateModified%22%3A%222021-11-03T19%3A22%3A50Z%22%7D%7D%2C%7B%22key%22%3A%22H3SKR22B%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Li%20et%20al.%22%2C%22parsedDate%22%3A%222018-09-26%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELi%2C%20L.%2C%20Tao%2C%20G.%2C%20Hill%2C%20M.%20C.%20et%20al.%20%282018%29.%20Pitx2%20maintains%20mitochondrial%20function%20during%20regeneration%20to%20prevent%20myocardial%20fat%20deposition.%20%3Ci%3EDevelopment%3C%5C%2Fi%3E%20%3Ci%3E145%3C%5C%2Fi%3E.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1242%5C%2Fdev.168609%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1242%5C%2Fdev.168609%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Pitx2%20maintains%20mitochondrial%20function%20during%20regeneration%20to%20prevent%20myocardial%20fat%20deposition%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lele%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ge%22%2C%22lastName%22%3A%22Tao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%20C.%22%2C%22lastName%22%3A%22Hill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22Loss%20of%20the%20paired-like%20homeodomain%20transcription%20factor%202%20%28Pitx2%29%20in%20cardiomyocytes%20predisposes%20mice%20to%20atrial%20fibrillation%20and%20compromises%20neonatal%20regenerative%20capacity.%20In%20addition%2C%20Pitx2%20gain-of-function%20protects%20mature%20cardiomyocytes%20from%20ischemic%20injury%20and%20promotes%20heart%20repair.%20Here%2C%20we%20characterized%20the%20long-term%20myocardial%20phenotype%20following%20myocardial%20infarction%20%28MI%29%20in%20Pitx2%20conditional-knockout%20%28Pitx2%20CKO%29%20mice.%20We%20found%20adipose-like%20tissue%20in%20Pitx2%20CKO%20hearts%2060%5Cu2005days%20after%20MI%20induced%20surgically%20at%20postnatal%20day%202%20but%20not%20at%20day%208.%20Molecular%20and%20cellular%20analyses%20showed%20the%20onset%20of%20adipogenic%20signaling%20in%20mutant%20hearts%20after%20MI.%20Lineage%20tracing%20experiments%20showed%20a%20non-cardiomyocyte%20origin%20of%20the%20de%20novo%20adipose-like%20tissue.%20Interestingly%2C%20we%20found%20that%20Pitx2%20promotes%20mitochondrial%20function%20through%20its%20gene%20regulatory%20network%2C%20and%20that%20the%20knockdown%20of%20a%20key%20mitochondrial%20Pitx2%20target%20gene%2C%20Cox7c%2C%20also%20leads%20to%20the%20accumulation%20of%20myocardial%20fat%20tissue.%20Single-nuclei%20RNA-seq%20revealed%20that%20Pitx2-deficient%20hearts%20were%20oxidatively%20stressed.%20Our%20findings%20reveal%20a%20role%20for%20Pitx2%20in%20maintaining%20proper%20cardiac%20cellular%20composition%20during%20heart%20regeneration%20via%20the%20maintenance%20of%20proper%20mitochondrial%20structure%20and%20function.%22%2C%22date%22%3A%22Sep%2026%2C%202018%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1242%5C%2Fdev.168609%22%2C%22ISSN%22%3A%221477-9129%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22SS2CP8WX%22%5D%2C%22dateModified%22%3A%222018-11-12T20%3A16%3A07Z%22%7D%7D%2C%7B%22key%22%3A%22EHNYGYZF%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Xiao%20et%20al.%22%2C%22parsedDate%22%3A%222018-04-23%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EXiao%2C%20Y.%2C%20Hill%2C%20M.%20C.%2C%20Zhang%2C%20M.%20et%20al.%20%282018%29.%20Hippo%20signaling%20plays%20an%20essential%20role%20in%20cell%20state%20transitions%20during%20cardiac%20fibroblast%20development.%20%3Ci%3EDev%20Cell%3C%5C%2Fi%3E%20%3Ci%3E45%3C%5C%2Fi%3E%2C%20153-169.e6.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.devcel.2018.03.019%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1016%5C%2Fj.devcel.2018.03.019%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Hippo%20signaling%20plays%20an%20essential%20role%20in%20cell%20state%20transitions%20during%20cardiac%20fibroblast%20development%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yang%22%2C%22lastName%22%3A%22Xiao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%20C.%22%2C%22lastName%22%3A%22Hill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Thomas%20J.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Suya%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Alexander%20R.%22%2C%22lastName%22%3A%22Moise%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Joshua%20D.%22%2C%22lastName%22%3A%22Wythe%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22During%20development%2C%20progenitors%20progress%20through%20transition%20states.%20The%20cardiac%20epicardium%20contains%20progenitors%20of%20essential%20non-cardiomyocytes.%20The%20Hippo%20pathway%2C%20a%20kinase%20cascade%20that%20inhibits%20the%20Yap%20transcriptional%20co-factor%2C%20controls%20organ%20size%20in%20developing%20hearts.%20Here%2C%20we%20investigated%20Hippo%20kinases%20Lats1%20and%20Lats2%20in%20epicardial%20diversification.%20Epicardial-specific%20deletion%20of%20Lats1%5C%2F2%20was%20embryonic%20lethal%2C%20and%20mutant%20embryos%20had%20defective%20coronary%20vasculature%20remodeling.%20Single-cell%20RNA%20sequencing%20revealed%20that%20Lats1%5C%2F2%20mutant%20cells%20failed%20to%20activate%20fibroblast%20differentiation%20but%20remained%20in%20an%20intermediate%20cell%20state%20with%20both%20epicardial%20and%20fibroblast%20characteristics.%20Lats1%5C%2F2%20mutant%20cells%20displayed%20an%20arrested%20developmental%20trajectory%20with%20persistence%20of%20epicardial%20markers%20and%20expanded%20expression%20of%20Yap%20targets%20Dhrs3%2C%20an%20inhibitor%20of%20retinoic%20acid%20synthesis%2C%20and%20Dpp4%2C%20a%20protease%20that%20modulates%20extracellular%20matrix%20%28ECM%29%20composition.%20Genetic%20and%20pharmacologic%20manipulation%20revealed%20that%20Yap%20inhibits%20fibroblast%20differentiation%2C%20prolonging%20a%20subepicardial-like%20cell%20state%2C%20and%20promotes%20expression%20of%20matricellular%20factors%2C%20such%20as%20Dpp4%2C%20that%20define%20ECM%20characteristics.%22%2C%22date%22%3A%22Apr%2023%2C%202018%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1016%5C%2Fj.devcel.2018.03.019%22%2C%22ISSN%22%3A%221878-1551%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22SS2CP8WX%22%5D%2C%22dateModified%22%3A%222018-05-08T17%3A54%3A14Z%22%7D%7D%2C%7B%22key%22%3A%22CFRMY83H%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Leach%20et%20al.%22%2C%22parsedDate%22%3A%222017-10%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ELeach%2C%20J.%20P.%2C%20Heallen%2C%20T.%2C%20Zhang%2C%20M.%20et%20al.%20%282017%29.%20Hippo%20pathway%20deficiency%20reverses%20systolic%20heart%20failure%20after%20infarction.%20%3Ci%3ENature%3C%5C%2Fi%3E%20%3Ci%3E550%3C%5C%2Fi%3E%2C%20260%26%23x2013%3B264.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fnature24045%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fnature24045%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Hippo%20pathway%20deficiency%20reverses%20systolic%20heart%20failure%20after%20infarction%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%20P.%22%2C%22lastName%22%3A%22Leach%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Todd%22%2C%22lastName%22%3A%22Heallen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mahdis%22%2C%22lastName%22%3A%22Rahmani%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Matthew%20C.%22%2C%22lastName%22%3A%22Hill%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ana%22%2C%22lastName%22%3A%22Segura%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20T.%22%2C%22lastName%22%3A%22Willerson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22Mammalian%20organs%20vary%20widely%20in%20regenerative%20capacity.%20Poorly%20regenerative%20organs%2C%20such%20as%20the%20heart%20are%20particularly%20vulnerable%20to%20organ%20failure.%20Once%20established%2C%20heart%20failure%20commonly%20results%20in%20mortality.%20The%20Hippo%20pathway%2C%20a%20kinase%20cascade%20that%20prevents%20adult%20cardiomyocyte%20proliferation%20and%20regeneration%2C%20is%20upregulated%20in%20human%20heart%20failure.%20Here%20we%20show%20that%20deletion%20of%20the%20Hippo%20pathway%20component%20Salvador%20%28Salv%29%20in%20mouse%20hearts%20with%20established%20ischaemic%20heart%20failure%20after%20myocardial%20infarction%20induces%20a%20reparative%20genetic%20program%20with%20increased%20scar%20border%20vascularity%2C%20reduced%20fibrosis%2C%20and%20recovery%20of%20pumping%20function%20compared%20with%20controls.%20Using%20translating%20ribosomal%20affinity%20purification%2C%20we%20isolate%20cardiomyocyte-specific%20translating%20messenger%20RNA.%20Hippo-deficient%20cardiomyocytes%20have%20increased%20expression%20of%20proliferative%20genes%20and%20stress%20response%20genes%2C%20such%20as%20the%20mitochondrial%20quality%20control%20gene%2C%20Park2.%20Genetic%20studies%20indicate%20that%20Park2%20is%20essential%20for%20heart%20repair%2C%20suggesting%20a%20requirement%20for%20mitochondrial%20quality%20control%20in%20regenerating%20myocardium.%20Gene%20therapy%20with%20a%20virus%20encoding%20Salv%20short%20hairpin%20RNA%20improves%20heart%20function%20when%20delivered%20at%20the%20time%20of%20infarct%20or%20after%20ischaemic%20heart%20failure%20following%20myocardial%20infarction%20was%20established.%20Our%20findings%20indicate%20that%20the%20failing%20heart%20has%20a%20previously%20unrecognized%20reparative%20capacity%20involving%20more%20than%20cardiomyocyte%20renewal.%22%2C%22date%22%3A%22Oct%202017%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fnature24045%22%2C%22ISSN%22%3A%221476-4687%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22NNUFWYNJ%22%2C%227IGCL8QC%22%2C%22QH7R47P9%22%2C%22SS2CP8WX%22%2C%22558WQRIW%22%5D%2C%22dateModified%22%3A%222018-05-02T20%3A38%3A55Z%22%7D%7D%2C%7B%22key%22%3A%22GFYMAZ24%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Morikawa%20et%20al.%22%2C%22parsedDate%22%3A%222017-07-13%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EMorikawa%3C%5C%2Fstrong%3E%2C%20Y.%2C%20Heallen%2C%20T.%2C%20Leach%2C%20J.%20et%20al.%20%282017%29.%20Dystrophin-glycoprotein%20complex%20sequesters%20Yap%20to%20inhibit%20cardiomyocyte%20proliferation.%20%3Ci%3ENature%3C%5C%2Fi%3E%20%3Ci%3E547%3C%5C%2Fi%3E%2C%20227%26%23x2013%3B231.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fnature22979%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fnature22979%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Dystrophin-glycoprotein%20complex%20sequesters%20Yap%20to%20inhibit%20cardiomyocyte%20proliferation%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Todd%22%2C%22lastName%22%3A%22Heallen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%22%2C%22lastName%22%3A%22Leach%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yang%22%2C%22lastName%22%3A%22Xiao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22The%20regenerative%20capacity%20of%20the%20adult%20mammalian%20heart%20is%20limited%2C%20because%20of%20the%20reduced%20ability%20of%20cardiomyocytes%20to%20progress%20through%20mitosis.%20Endogenous%20cardiomyocytes%20have%20regenerative%20capacity%20at%20birth%20but%20this%20capacity%20is%20lost%20postnatally%2C%20with%20subsequent%20organ%20growth%20occurring%20through%20cardiomyocyte%20hypertrophy.%20The%20Hippo%20pathway%2C%20a%20conserved%20kinase%20cascade%2C%20inhibits%20cardiomyocyte%20proliferation%20in%20the%20developing%20heart%20to%20control%20heart%20size%20and%20prevents%20regeneration%20in%20the%20adult%20heart.%20The%20dystrophin-glycoprotein%20complex%20%28DGC%29%2C%20a%20multicomponent%20transmembrane%20complex%20linking%20the%20actin%20cytoskeleton%20to%20extracellular%20matrix%2C%20is%20essential%20for%20cardiomyocyte%20homeostasis.%20DGC%20deficiency%20in%20humans%20results%20in%20muscular%20dystrophy%2C%20including%20the%20lethal%20Duchenne%20muscular%20dystrophy.%20Here%20we%20show%20that%20the%20DGC%20component%20dystroglycan%201%20%28Dag1%29%20directly%20binds%20to%20the%20Hippo%20pathway%20effector%20Yap%20to%20inhibit%20cardiomyocyte%20proliferation%20in%20mice.%20The%20Yap-Dag1%20interaction%20was%20enhanced%20by%20Hippo-induced%20Yap%20phosphorylation%2C%20revealing%20a%20connection%20between%20Hippo%20pathway%20function%20and%20the%20DGC.%20After%20injury%2C%20Hippo-deficient%20postnatal%20mouse%20hearts%20maintained%20organ%20size%20control%20by%20repairing%20the%20defect%20with%20correct%20dimensions%2C%20whereas%20postnatal%20hearts%20deficient%20in%20both%20Hippo%20and%20the%20DGC%20showed%20cardiomyocyte%20overproliferation%20at%20the%20injury%20site.%20In%20the%20hearts%20of%20mature%20Mdx%20mice%20%28which%20have%20a%20point%20mutation%20in%20Dmd%29-a%20model%20of%20Duchenne%20muscular%20dystrophy-Hippo%20deficiency%20protected%20against%20overload-induced%20heart%20failure.%22%2C%22date%22%3A%22Jul%2013%2C%202017%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fnature22979%22%2C%22ISSN%22%3A%221476-4687%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22QH7R47P9%22%2C%22SS2CP8WX%22%5D%2C%22dateModified%22%3A%222018-05-04T20%3A38%3A37Z%22%7D%7D%2C%7B%22key%22%3A%22A3SZ7288%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Tao%20et%20al.%22%2C%22parsedDate%22%3A%222016-06-02%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3ETao%2C%20G.%2C%20Kahr%2C%20P.%20C.%2C%20%3Cstrong%3EMorikawa%3C%5C%2Fstrong%3E%2C%20Y.%20et%20al.%20%282016%29.%20Pitx2%20promotes%20heart%20repair%20by%20activating%20the%20antioxidant%20response%20after%20cardiac%20injury.%20%3Ci%3ENature%3C%5C%2Fi%3E%20%3Ci%3E534%3C%5C%2Fi%3E%2C%20119%26%23x2013%3B123.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fnature17959%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1038%5C%2Fnature17959%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Pitx2%20promotes%20heart%20repair%20by%20activating%20the%20antioxidant%20response%20after%20cardiac%20injury%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ge%22%2C%22lastName%22%3A%22Tao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Peter%20C.%22%2C%22lastName%22%3A%22Kahr%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Mahdis%22%2C%22lastName%22%3A%22Rahmani%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Todd%20R.%22%2C%22lastName%22%3A%22Heallen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Lele%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Zhao%22%2C%22lastName%22%3A%22Sun%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Eric%20N.%22%2C%22lastName%22%3A%22Olson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Brad%20A.%22%2C%22lastName%22%3A%22Amendt%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22Myocardial%20infarction%20results%20in%20compromised%20myocardial%20function%20and%20heart%20failure%20owing%20to%20insufficient%20cardiomyocyte%20self-renewal.%20Unlike%20many%20vertebrates%2C%20mammalian%20hearts%20have%20only%20a%20transient%20neonatal%20renewal%20capacity.%20Reactivating%20primitive%20reparative%20ability%20in%20the%20mature%20mammalian%20heart%20requires%20knowledge%20of%20the%20mechanisms%20that%20promote%20early%20heart%20repair.%20By%20testing%20an%20established%20Hippo-deficient%20heart%20regeneration%20mouse%20model%20for%20factors%20that%20promote%20renewal%2C%20here%20we%20show%20that%20the%20expression%20of%20Pitx2%20is%20induced%20in%20injured%2C%20Hippo-deficient%20ventricles.%20Pitx2-deficient%20neonatal%20mouse%20hearts%20failed%20to%20repair%20after%20apex%20resection%2C%20whereas%20adult%20mouse%20cardiomyocytes%20with%20Pitx2%20gain-of-function%20efficiently%20regenerated%20after%20myocardial%20infarction.%20Genomic%20analyses%20indicated%20that%20Pitx2%20activated%20genes%20encoding%20electron%20transport%20chain%20components%20and%20reactive%20oxygen%20species%20scavengers.%20A%20subset%20of%20Pitx2%20target%20genes%20was%20cooperatively%20regulated%20with%20the%20Hippo%20pathway%20effector%20Yap.%20Furthermore%2C%20Nrf2%2C%20a%20regulator%20of%20the%20antioxidant%20response%2C%20directly%20regulated%20the%20expression%20and%20subcellular%20localization%20of%20Pitx2.%20Pitx2%20mutant%20myocardium%20had%20increased%20levels%20of%20reactive%20oxygen%20species%2C%20while%20antioxidant%20supplementation%20suppressed%20the%20Pitx2%20loss-of-function%20phenotype.%20These%20findings%20reveal%20a%20genetic%20pathway%20activated%20by%20tissue%20damage%20that%20is%20essential%20for%20cardiac%20repair.%22%2C%22date%22%3A%22Jun%2002%2C%202016%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1038%5C%2Fnature17959%22%2C%22ISSN%22%3A%221476-4687%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22QH7R47P9%22%2C%22SS2CP8WX%22%5D%2C%22dateModified%22%3A%222018-05-04T20%3A41%3A44Z%22%7D%7D%2C%7B%22key%22%3A%22JHWJYIKB%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Morikawa%20et%20al.%22%2C%22parsedDate%22%3A%222015-05-05%22%2C%22numChildren%22%3A1%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3E%3Cstrong%3EMorikawa%3C%5C%2Fstrong%3E%2C%20Y.%2C%20Zhang%2C%20M.%2C%20Heallen%2C%20T.%20et%20al.%20%282015%29.%20Actin%20cytoskeletal%20remodeling%20with%20protrusion%20formation%20is%20essential%20for%20heart%20regeneration%20in%20Hippo-deficient%20mice.%20%3Ci%3ESci%20Signal%3C%5C%2Fi%3E%20%3Ci%3E8%3C%5C%2Fi%3E%2C%20ra41.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscisignal.2005781%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1126%5C%2Fscisignal.2005781%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Actin%20cytoskeletal%20remodeling%20with%20protrusion%20formation%20is%20essential%20for%20heart%20regeneration%20in%20Hippo-deficient%20mice%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Min%22%2C%22lastName%22%3A%22Zhang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Todd%22%2C%22lastName%22%3A%22Heallen%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22John%22%2C%22lastName%22%3A%22Leach%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ge%22%2C%22lastName%22%3A%22Tao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yang%22%2C%22lastName%22%3A%22Xiao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yan%22%2C%22lastName%22%3A%22Bai%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Wei%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20T.%22%2C%22lastName%22%3A%22Willerson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%5D%2C%22abstractNote%22%3A%22The%20mammalian%20heart%20regenerates%20poorly%2C%20and%20damage%20commonly%20leads%20to%20heart%20failure.%20Hippo%20signaling%20is%20an%20evolutionarily%20conserved%20kinase%20cascade%20that%20regulates%20organ%20size%20during%20development%20and%20prevents%20adult%20mammalian%20cardiomyocyte%20regeneration%20by%20inhibiting%20the%20transcriptional%20coactivator%20Yap%2C%20which%20also%20responds%20to%20mechanical%20signaling%20in%20cultured%20cells%20to%20promote%20cell%20proliferation.%20To%20identify%20Yap%20target%20genes%20that%20are%20activated%20during%20cardiomyocyte%20renewal%20and%20regeneration%2C%20we%20performed%20Yap%20chromatin%20immunoprecipitation%20sequencing%20%28ChIP-Seq%29%20and%20mRNA%20expression%20profiling%20in%20Hippo%20signaling-deficient%20mouse%20hearts.%20We%20found%20that%20Yap%20directly%20regulated%20genes%20encoding%20cell%20cycle%20progression%20proteins%2C%20as%20well%20as%20genes%20encoding%20proteins%20that%20promote%20F-actin%20polymerization%20and%20that%20link%20the%20actin%20cytoskeleton%20to%20the%20extracellular%20matrix.%20Included%20in%20the%20latter%20group%20were%20components%20of%20the%20dystrophin%20glycoprotein%20complex%2C%20a%20large%20molecular%20complex%20that%2C%20when%20defective%2C%20results%20in%20muscular%20dystrophy%20in%20humans.%20Cardiomyocytes%20near%20the%20scar%20tissue%20of%20injured%20Hippo%20signaling-deficient%20mouse%20hearts%20showed%20cellular%20protrusions%20suggestive%20of%20cytoskeletal%20remodeling.%20The%20hearts%20of%20mdx%20mutant%20mice%2C%20which%20lack%20functional%20dystrophin%20and%20are%20a%20model%20for%20muscular%20dystrophy%2C%20showed%20impaired%20regeneration%20and%20cytoskeleton%20remodeling%2C%20but%20normal%20cardiomyocyte%20proliferation%2C%20after%20injury.%20Our%20data%20showed%20that%2C%20in%20addition%20to%20genes%20encoding%20cell%20cycle%20progression%20proteins%2C%20Yap%20regulated%20genes%20that%20enhance%20cytoskeletal%20remodeling.%20Thus%2C%20blocking%20the%20Hippo%20pathway%20input%20to%20Yap%20may%20tip%20the%20balance%20so%20that%20Yap%20responds%20to%20mechanical%20changes%20associated%20with%20heart%20injury%20to%20promote%20repair.%22%2C%22date%22%3A%22May%2005%2C%202015%22%2C%22language%22%3A%22eng%22%2C%22DOI%22%3A%2210.1126%5C%2Fscisignal.2005781%22%2C%22ISSN%22%3A%221937-9145%22%2C%22url%22%3A%22%22%2C%22collections%22%3A%5B%22NNUFWYNJ%22%2C%227IGCL8QC%22%2C%22QH7R47P9%22%2C%22SS2CP8WX%22%5D%2C%22dateModified%22%3A%222018-05-02T20%3A21%3A23Z%22%7D%7D%2C%7B%22key%22%3A%227QPB4VDG%22%2C%22library%22%3A%7B%22id%22%3A4862227%7D%2C%22meta%22%3A%7B%22creatorSummary%22%3A%22Wang%20et%20al.%22%2C%22parsedDate%22%3A%222015-03-06%22%2C%22numChildren%22%3A0%7D%2C%22bib%22%3A%22%3Cdiv%20class%3D%5C%22csl-bib-body%5C%22%20style%3D%5C%22line-height%3A%201.35%3B%20padding-left%3A%201em%3B%20text-indent%3A-1em%3B%5C%22%3E%5Cn%20%20%3Cdiv%20class%3D%5C%22csl-entry%5C%22%3EWang%2C%20S.%2C%20Lopez%2C%20A.%20L.%2C%20%3Cstrong%3EMorikawa%3C%5C%2Fstrong%3E%2C%20Y.%20et%20al.%20%282015%29.%20Quantitative%20shear%20wave%20imaging%20optical%20coherence%20tomography%20for%20noncontact%20mechanical%20characterization%20of%20myocardium%20K.%20V.%20Larin%20and%20D.%20D.%20Sampson%20%28eds.%29%2C.%20%2C%2093270F.%20%3Ca%20class%3D%27zp-DOIURL%27%20href%3D%27https%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1117%5C%2F12.2078376%27%3Ehttps%3A%5C%2F%5C%2Fdoi.org%5C%2F10.1117%5C%2F12.2078376%3C%5C%2Fa%3E.%3C%5C%2Fdiv%3E%5Cn%3C%5C%2Fdiv%3E%22%2C%22data%22%3A%7B%22itemType%22%3A%22journalArticle%22%2C%22title%22%3A%22Quantitative%20shear%20wave%20imaging%20optical%20coherence%20tomography%20for%20noncontact%20mechanical%20characterization%20of%20myocardium%22%2C%22creators%22%3A%5B%7B%22creatorType%22%3A%22editor%22%2C%22firstName%22%3A%22Kirill%20V.%22%2C%22lastName%22%3A%22Larin%22%7D%2C%7B%22creatorType%22%3A%22editor%22%2C%22firstName%22%3A%22David%20D.%22%2C%22lastName%22%3A%22Sampson%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Shang%22%2C%22lastName%22%3A%22Wang%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Andrew%20L.%22%2C%22lastName%22%3A%22Lopez%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Yuka%22%2C%22lastName%22%3A%22Morikawa%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Ge%22%2C%22lastName%22%3A%22Tao%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Jiasong%22%2C%22lastName%22%3A%22Li%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Irina%20V.%22%2C%22lastName%22%3A%22Larina%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22James%20F.%22%2C%22lastName%22%3A%22Martin%22%7D%2C%7B%22creatorType%22%3A%22author%22%2C%22firstName%22%3A%22Kirill%20V.%22%2C%22lastName%22%3A%22Larin%22%7D%5D%2C%22abstractNote%22%3A%22%22%2C%22date%22%3A%222015-3-6%22%2C%22language%22%3A%22%22%2C%22DOI%22%3A%2210.1117%5C%2F12.2078376%22%2C%22ISSN%22%3A%22%22%2C%22url%22%3A%22http%3A%5C%2F%5C%2Fproceedings.spiedigitallibrary.org%5C%2Fproceeding.aspx%3Fdoi%3D10.1117%5C%2F12.2078376%22%2C%22collections%22%3A%5B%227IGCL8QC%22%2C%22SS2CP8WX%22%5D%2C%22dateModified%22%3A%222018-05-23T13%3A56%3A42Z%22%7D%7D%5D%7D
Hill, M. C., Kadow, Z. A., Long, H. et al. (2022). Integrated multi-omic characterization of congenital heart disease. Nature. https://doi.org/10.1038/s41586-022-04989-3.
Aharonov, A., Shakked, A., Umansky, K. B. et al. (2020). ERBB2 drives YAP activation and EMT-like processes during cardiac regeneration. Nat Cell Biol 22, 1346–1356. https://doi.org/10.1038/s41556-020-00588-4.
Monroe, T. O., Hill, M. C., Morikawa, Y. et al. (2019). YAP partially reprograms chromatin accessibility to directly induce adult cardiogenesis in vivo. Dev Cell 48, 765-779.e7. https://doi.org/10.1016/j.devcel.2019.01.017.
Li, L., Tao, G., Hill, M. C. et al. (2018). Pitx2 maintains mitochondrial function during regeneration to prevent myocardial fat deposition. Development 145. https://doi.org/10.1242/dev.168609.
Xiao, Y., Hill, M. C., Zhang, M. et al. (2018). Hippo signaling plays an essential role in cell state transitions during cardiac fibroblast development. Dev Cell 45, 153-169.e6. https://doi.org/10.1016/j.devcel.2018.03.019.
Leach, J. P., Heallen, T., Zhang, M. et al. (2017). Hippo pathway deficiency reverses systolic heart failure after infarction. Nature 550, 260–264. https://doi.org/10.1038/nature24045.
Morikawa, Y., Heallen, T., Leach, J. et al. (2017). Dystrophin-glycoprotein complex sequesters Yap to inhibit cardiomyocyte proliferation. Nature 547, 227–231. https://doi.org/10.1038/nature22979.
Tao, G., Kahr, P. C., Morikawa, Y. et al. (2016). Pitx2 promotes heart repair by activating the antioxidant response after cardiac injury. Nature 534, 119–123. https://doi.org/10.1038/nature17959.
Morikawa, Y., Zhang, M., Heallen, T. et al. (2015). Actin cytoskeletal remodeling with protrusion formation is essential for heart regeneration in Hippo-deficient mice. Sci Signal 8, ra41. https://doi.org/10.1126/scisignal.2005781.
Wang, S., Lopez, A. L., Morikawa, Y. et al. (2015). Quantitative shear wave imaging optical coherence tomography for noncontact mechanical characterization of myocardium K. V. Larin and D. D. Sampson (eds.),. , 93270F. https://doi.org/10.1117/12.2078376.