Single-cell transcriptome and epigenomic reprogramming of cardiomyocyte-derived cardiac progenitor cells.
The molecular basis underlying the dedifferentiation of mammalian adult cardiomyocytes (ACMs) into myocyte-derived cardiac progenitor cells (mCPCs) during cardiac tissue regeneration is poorly understood. We present data integrating single-cell transcriptome and whole-genome DNA methylome analyses of mouse mCPCs to understand the epigenomic reprogramming governing their intrinsic cellular plasticity. Compared to parental cardiomyocytes, mCPCs display epigenomic reprogramming with many differentially-methylated regions, both hypermethylated and hypomethylated, across the entire genome. Correlating well with the methylome, our single-cell transcriptomic data show that the genes encoding cardiac structure and function proteins are remarkably down-regulated in mCPCs, while those for cell cycle, proliferation, and stemness are significantly up-regulated. In addition, implanting mCPCs into infarcted mouse myocardium improves cardiac function with augmented left ventricular ejection fraction. This dataset suggests that the cellular plasticity of mammalian cardiomyocytes is the result of a well-orchestrated epigenomic reprogramming and a subsequent global transcriptomic alteration. Understanding cardiomyocyte epigenomic reprogramming may enable the design of future clinical therapies that induce cardiac regeneration, and prevent heart failure.
Center for Genomics &Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA.
Xin
X
Chen
Center for Genomics &Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA.
Tushar
0000-0002-8778-7998
T
Chakravarty
Division of Cardiology, Department of Medicine, and Center for Cardiovascular Biology, and Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington 98109, USA.
Yiqiang
0000-0003-0691-6645
Y
Zhang
CardioDx, Inc., 600 Saginaw Drive, Redwood City, California 94063, USA.
Xiaojin
X
Li
Division of Periodontology, Diagnostic Sciences &Dental Hygiene &Biomedical Sciences, Herman Ostrow School of Dentistry, and Norris Cancer Center, University of Southern California, Los Angeles, Los Angeles, California 90089, USA.
Jiang F
JF
Zhong
Center for Genomics &Department of Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, California 92350, USA.
Charles
C
Wang
D000818:Animals; D057890:Epigenomics; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D013234:Stem Cells; D059467:Transcriptome