@article{6f1c4fe8d0df4cc5885522fbd8a16121,
title = "Analysis of cardiomyocyte clonal expansion during mouse heart development and injury",
abstract = "The cellular mechanisms driving cardiac tissue formation remain poorly understood, largely due to the structural and functional complexity of the heart. It is unclear whether newly generated myocytes originate from cardiac stem/progenitor cells or from pre-existing cardiomyocytes that re-enter the cell cycle. Here, we identify the source of new cardiomyocytes during mouse development and after injury. Our findings suggest that cardiac progenitors maintain proliferative potential and are the main source of cardiomyocytes during development; however, the onset of αMHC expression leads to reduced cycling capacity. Single-cell RNA sequencing reveals a proliferative, {"}progenitor-like{"} population abundant in early embryonic stages that decreases to minimal levels postnatally. Furthermore, cardiac injury by ligation of the left anterior descending artery was found to activate cardiomyocyte proliferation in neonatal but not adult mice. Our data suggest that clonal dominance of differentiating progenitors mediates cardiac development, while a distinct subpopulation of cardiomyocytes may have the potential for limited proliferation during late embryonic development and shortly after birth.",
author = "Sereti, {Konstantina Ioanna} and Nguyen, {Ngoc B.} and Paniz Kamran and Peng Zhao and Sara Ranjbarvaziri and Shuin Park and Shan Sabri and Engel, {James L.} and Kevin Sung and Kulkarni, {Rajan P.} and Yichen Ding and Hsiai, {Tzung K.} and Kathrin Plath and Jason Ernst and Debashis Sahoo and Mikkola, {Hanna K.A.} and Iruela-Arispe, {M. Luisa} and Reza Ardehali",
note = "Funding Information: We would like to thank Dr. Matt Schibler for assistance with confocal microscopy, completed at the UCLA CNSI Advanced light microscopy/Spectroscopy Shared Resource Facility, supported by NIH-NCRR shared resources grant (CJX1-443835-WS-29646) and NSF Major Research Instrumentation grant (CHE-0722519). We also thank Dr. Esteban Fernandez for his help with 3D reconstruction and video processing, Dr. Cheng-Han Chen for help with tamoxifen serum levels measurements and all Ardehali lab members for discussions and suggestions. This work was supported in part by grants from the California Institute for Regenerative Medicine (CIRM) (RN3-06378) (R.A.), the National Institutes of Health (NIH) DP2 HL127728 (R.A.), the American Heart Association (AHA-BGA 12BGIA8960008) (R.A.) and Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA Research Award (R.A. and H.M.), Scholars in Translational Medicine Program (R.A.), and UCLA BSCRC-Rose Hills Foundation Training Program (S.S.), the American Heart Association (14GRNT20480340) (H.M.), NIH R00-CA151673 and Department of Defense grant (W81XWH-10-1-0500) (D.S.), CIRM training grant (TG2-01169) (K.I.S.), and the Sarnoff Cardiovascular Research Foundation (N.B.N.). Publisher Copyright: {\textcopyright} 2018 The Author(s). Copyright: Copyright 2018 Elsevier B.V., All rights reserved.",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41467-018-02891-z",
language = "English (US)",
volume = "9",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}