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Analysis of cardiomyocyte clonal expansion during mouse heart development and injury

Konstantina-Ioanna Sereti, Ngoc B. Nguyen, Paniz Kamran, Peng Zhao, Sara Ranjbarvaziri, Shuin Park, Shan Sabri, James L. Engel, Kevin Sung, Rajan P. Kulkarni, Yichen Ding, Tzung K. Hsiai, Kathrin Plath, Jason Ernst, Debashis Sahoo, Hanna K.A. Mikkola, M. Luisa Iruela-Arispe and Reza Ardehali ()
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Konstantina-Ioanna Sereti: University of California, Los Angeles
Ngoc B. Nguyen: University of California, Los Angeles
Paniz Kamran: University of California, Los Angeles
Peng Zhao: University of California, Los Angeles
Sara Ranjbarvaziri: University of California, Los Angeles
Shuin Park: University of California, Los Angeles
Shan Sabri: University of California, Los Angeles
James L. Engel: University of California, Los Angeles
Kevin Sung: University of California, Los Angeles
Rajan P. Kulkarni: Jonsson Comprehensive Cancer Center
Yichen Ding: University of California, Los Angeles
Tzung K. Hsiai: University of California, Los Angeles
Kathrin Plath: University of California, Los Angeles
Jason Ernst: University of California, Los Angeles
Debashis Sahoo: University of California San Diego
Hanna K.A. Mikkola: University of California, Los Angeles
M. Luisa Iruela-Arispe: University of California, Los Angeles
Reza Ardehali: University of California, Los Angeles

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-02891-z

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DOI: 10.1038/s41467-018-02891-z

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