Epigenetic delineation of the earliest cardiac lineage segregation by single-cell multi-omics
Epigenetic delineation of the earliest cardiac lineage segregation by single-cell multi-omics
Abstract The mammalian heart is formed from multiple mesoderm-derived cell lineages. However, it remains largely unknown when and how the specification of mesoderm towards cardiac lineages is determined. Here, we systematically depict the transcriptional trajectories toward cardiomyocyte in early mouse embryo, and characterize the epigenetic landscapes underlying the early mesodermal lineage specification by single-cell multi-omics analyses. The analyses also reveal distinct core regulatory networks (CRN) in controlling specification of mesodermal lineages. We further demonstrate the essential role HAND1 and FOXF1 in driving the earliest cardiac progenitors specification. These key transcription factors occupy at distinct enhancers, but function synergistically and hierarchically to regulate the expression of cardiac-specific genes. In addition, HAND1 is required for exiting from the nascent mesoderm program, while FOXF1 is essential for driving cardiac differentiation during MJH specification. Our findings establish transcriptional and epigenetic determinants specifying the early cardiac lineage, providing insights for the investigation of congenital heart defects.
Wu Chen、Zheng Weiheng、Zhu Shiqi、He Jingjing、Xie Peng、Pan Qingyun、Xie Wei、Lin Chengqi、Fang Ke、Luo Zhuojuan、Zheng Yanying、Yang Zhongzhou、Jing Naihe、Zhong Tao P.、Jiang Xu、Si Shuhan、Wei Ke、Fan Wenli、Yang Zhongzhou、Yang Yi
Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, School of Biological Science and Medical Engineering, Southeast UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, School of Biological Science and Medical Engineering, Southeast UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, School of Biological Science and Medical Engineering, Southeast University||Co-innovation Center of Neuroregeneration, Nantong UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityCo-innovation Center of Neuroregeneration, Nantong University||Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityCo-innovation Center of Neuroregeneration, Nantong University||Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityCo-innovation Center of Neuroregeneration, Nantong University||Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityState Key Laboratory of Pharmaceutical Biotechnology, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing UniversityGuangzhou Laboratory||CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of SciencesShanghai Key Laboratory of Regulatory Biology, Institute of Molecular Medicine, School of Life Sciences, East China Normal UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast UniversityInstitute for Regenerative Medicine, Shanghai East Hospital, Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai Key Laboratory of Signaling and Disease Research, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Department of Molecular and Cellular Biology, Tongji UniversityState Key Laboratory of Pharmaceutical Biotechnology, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing UniversityState Key Laboratory of Pharmaceutical Biotechnology, Department of Cardiology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing UniversityBasic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Key Laboratory of Developmental Genes and Human Disease, School of Life Science and Technology, Southeast University
基础医学分子生物学细胞生物学
CardiogenesisSingle cell analysisEpigeneticsEnhancerHAND1
Wu Chen,Zheng Weiheng,Zhu Shiqi,He Jingjing,Xie Peng,Pan Qingyun,Xie Wei,Lin Chengqi,Fang Ke,Luo Zhuojuan,Zheng Yanying,Yang Zhongzhou,Jing Naihe,Zhong Tao P.,Jiang Xu,Si Shuhan,Wei Ke,Fan Wenli,Yang Zhongzhou,Yang Yi.Epigenetic delineation of the earliest cardiac lineage segregation by single-cell multi-omics[EB/OL].(2025-03-28)[2025-06-21].https://www.biorxiv.org/content/10.1101/2024.05.17.594655.点此复制
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