Molecular Signatures and Networks of Cardiomyocyte Differentiation in Humans and Mice

Yumei Wang; Na Yi; Yi Hu; Xianxiao Zhou; Hanyu Jiang; Qin Lin; Rou Chen; Huan Liu; Yanqiong Gu; Chang Tong; Min Lu; Junfang Zhang; Bin Zhang; Luying Peng; Li Li

Molecular Therapy: Nucleic Acids (Sep 2020)

Molecular Signatures and Networks of Cardiomyocyte Differentiation in Humans and Mice

Yumei Wang,
Na Yi,
Yi Hu,
Xianxiao Zhou,
Hanyu Jiang,
Qin Lin,
Rou Chen,
Huan Liu,
Yanqiong Gu,
Chang Tong,
Min Lu,
Junfang Zhang,
Bin Zhang,
Luying Peng,
Li Li

Affiliations

Yumei Wang: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China; Heart Health Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200092, China
Na Yi: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China; Heart Health Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200092, China
Yi Hu: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China; Heart Health Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200092, China
Xianxiao Zhou: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
Hanyu Jiang: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Qin Lin: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China; Heart Health Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200092, China
Rou Chen: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Huan Liu: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China; Heart Health Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200092, China
Yanqiong Gu: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Chang Tong: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Min Lu: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China
Junfang Zhang: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China
Bin Zhang: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Mount Sinai Center for Transformative Disease Modeling, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA; Icahn Institute for Data Science and Genomic Technology, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York, NY 10029, USA
Luying Peng: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China; Heart Health Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200092, China; Corresponding author: Luying Peng, Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
Li Li: Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Institute of Medical Genetics, Tongji University, Shanghai 200092, China; Department of Medical Genetics, Tongji University School of Medicine, Shanghai 200092, China; Heart Health Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China; Research Units of Origin and Regulation of Heart Rhythm, Chinese Academy of Medical Sciences, Shanghai 200092, China; Corresponding author: Li Li, Key Laboratory of Arrhythmias, Ministry of Education, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China.

Journal volume & issue: Vol. 21
pp. 696 – 711

Abstract

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Cardiomyocyte differentiation derived from embryonic stem cells (ESCs) is a complex process involving molecular regulation of multiple levels. In this study, we first identify and compare differentially expressed gene (DEG) signatures of ESC-derived cardiomyocyte differentiation (ESCDCD) in humans and mice. Then, the multiscale embedded gene co-expression network analysis (MEGENA) of the human ESCDCD dataset is performed to identify 212 significantly co-expressed gene modules, which capture well the regulatory information of cardiomyocyte differentiation. Three modules respectively involved in the regulation of stem cell pluripotency, Wnt, and calcium pathways are enriched in the DEG signatures of the differentiation phase transition in the two species. Three human-specific cardiomyocyte differentiation phase transition modules are identified. Moreover, the potential regulation mechanisms of transcription factors during cardiomyocyte differentiation are also illustrated. Finally, several novel key drivers of ESCDCD are identified with the evidence of their expression during mouse embryonic cardiomyocyte differentiation. Using an integrative network analysis, the core molecular signatures and gene subnetworks (modules) underlying cardiomyocyte lineage commitment are identified in both humans and mice. Our findings provide a global picture of gene-gene co-regulation and identify key regulators during ESCDCD.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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