c-JUN is a barrier in hESC to cardiomyocyte transition

Zhong, Hui1,3; Zhang, Ran1,2,4; Li, Guihuan2; Huang, Ping10; Zhang, Yudan4; Zhu, Jieying3; Kuang, Junqi5; Hutchins, Andrew P.6; Qin, Dajiang2,4,9; Zhu, Ping1,7,8; Pei, Duanqing5; Li, Dongwei1,2

2023-11-01

10.26508/lsa.202302121

LIFE SCIENCE ALLIANCE   影响因子和分区

2575-1077

Loss of c-JUN leads to early mouse embryonic death, possibly because of a failure to develop a normal cardiac system. How c-JUN regulates human cardiomyocyte cell fate remains unknown. Here, we used the in vitro differentiation of human pluripotent stem cells into cardiomyocytes to study the role of c-JUN. Surprisingly, the knockout of c-JUN improved cardiomyocyte generation, as determined by the number of TNNT2+ cells. ATAC-seq data showed that the c-JUN defect led to increased chromatin accessibility on critical regulatory elements related to cardiomyocyte development. ChIP-seq data showed that the knockout c-JUN increased RBBP5 and SETD1B expression, leading to improved H3K4me3 deposition on key genes that regulate cardiogenesis. The c-JUN KO phenotype could be copied using the histone demethylase inhibitor CPI-455, which also up-regulated H3K4me3 levels and increased cardiomyocyte generation. Single-cell RNA-seq data defined three cell branches, and knockout c-JUN activated more regulons that are related to cardiogenesis. In summary, our data demonstrated that c-JUN could regulate cardiomyocyte cell fate by modulating H3K4me3 modification and chromatin accessibility and shed light on how c-JUN regulates heart development in humans.

SCI

英语

其他

National Natural Science Foundation of China["32270574","32150710521","2018YFA0108700"] ; National Key Research and Development Program of China["2017YFA0105602","2020B12120600 52"] ; Guangdong Science and Technology Project["2022B1212010010","202201020379"] ; Guangzhou Key Laboratory of Biological Targeting Diagnosis and Therapy[DFJHBF202110] ; Youth Innovation Promotion of the Chinese Academy of Sciences[DFJHBF202111] ; Guangdong Cardiovascular Institute[2023A03J0045] ; High-level Hospital Construction Project[2023A04J0156] ; null[92068021] ; null[2019348] ; null[2020XXG002]

Life Sciences & Biomedicine - Other Topics

Biology

WOS:001056794000006

LIFE SCIENCE ALLIANCE LLC

Web of Science

1.Southern Med Univ, Guangdong Prov Peoples Hosp, Guangdong Cardiovasc Inst, Guangdong Acad Med Sci, Guangzhou, Peoples R China
2.Guangzhou Med Univ, Therapy & Rehabil Guangdong Higher Educ Inst, Key Lab Biol Targeting Diag, Affiliated Hosp 5, Guangzhou, Peoples R China
3.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Ctr Cell Lineage & Dev, CAS Key Lab Regenerat Biol, Guangzhou, Peoples R China
4.Bioland Lab, Guangzhou Regenerat Med & Hlth Guangdong Lab, Guangzhou, Peoples R China
5.Westlake Univ, Sch Life Sci, Lab Cell Fate Control, Hangzhou, Peoples R China
6.Southern Univ Sci & Technol, Sch Life Sci, Dept Syst Biol, Shenzhen, Peoples R China
7.Guangdong Prov Key Lab Pathogenesis, Targeted Prevent & Treatment Heart Dis, Guangzhou, Peoples R China
8.Guangzhou Key Lab Pathogenesis Targeted Prevent &, Guangzhou, Peoples R China
9.Chinese Acad Sci, Ctr Regenerat Med & Hlth, Hong Kong Inst Sci & Innovat, Hong Kong 999077, Peoples R China
10.Guangzhou Univ Chinese Med, Affiliated Hosp 2, Guangzhou, Peoples R China

Zhong, Hui,Zhang, Ran,Li, Guihuan,et al. c-JUN is a barrier in hESC to cardiomyocyte transition[J]. LIFE SCIENCE ALLIANCE,2023,6(11).

Zhong, Hui.,Zhang, Ran.,Li, Guihuan.,Huang, Ping.,Zhang, Yudan.,...&Li, Dongwei.(2023).c-JUN is a barrier in hESC to cardiomyocyte transition.LIFE SCIENCE ALLIANCE,6(11).

Zhong, Hui,et al."c-JUN is a barrier in hESC to cardiomyocyte transition".LIFE SCIENCE ALLIANCE 6.11(2023).