c-JUN is a barrier in hESC to cardiomyocyte transition.
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
11 2023
11 2023
Historique:
received:
27
04
2023
revised:
06
08
2023
accepted:
07
08
2023
medline:
23
8
2023
pubmed:
22
8
2023
entrez:
21
8
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37604584
pii: 6/11/e202302121
doi: 10.26508/lsa.202302121
pmc: PMC10442936
pii:
doi:
Substances chimiques
Chromatin
0
JUN protein, human
0
Proto-Oncogene Proteins c-jun
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023 Zhong et al.
Références
Cell Res. 2013 Oct;23(10):1172-86
pubmed: 24018375
Cell Stem Cell. 2012 Jan 6;10(1):16-28
pubmed: 22226352
Cell Stem Cell. 2008 Jul 3;3(1):55-68
pubmed: 18593559
Signal Transduct Target Ther. 2022 Jun 25;7(1):200
pubmed: 35752619
Nat Methods. 2017 Nov;14(11):1083-1086
pubmed: 28991892
Nat Genet. 2019 Jun;51(6):999-1010
pubmed: 31110351
Genes Dev. 2011 Apr 1;25(7):661-72
pubmed: 21460034
BMC Bioinformatics. 2011 Aug 04;12:323
pubmed: 21816040
Nat Biotechnol. 2013 Jul;31(7):615-22
pubmed: 23770639
Front Cell Dev Biol. 2021 Nov 25;9:793605
pubmed: 34901033
Nat Cell Biol. 2009 Aug;11(8):951-7
pubmed: 19620969
Circ Res. 2010 Dec 10;107(12):1414-27
pubmed: 21148448
Circ Res. 2020 Jun 5;126(12):1760-1778
pubmed: 32312172
Nat Commun. 2015 Sep 10;6:8243
pubmed: 26354680
Cell Stem Cell. 2011 Jul 8;9(1):24-36
pubmed: 21726831
BMC Bioinformatics. 2011 Dec 17;12:480
pubmed: 22177264
Dev Cell. 2003 Dec;5(6):877-89
pubmed: 14667410
PLoS One. 2013 Sep 10;8(9):e73294
pubmed: 24039904
Circ Res. 2012 Jul 20;111(3):344-58
pubmed: 22821908
Cell Stem Cell. 2019 Jul 3;25(1):87-102.e9
pubmed: 31271750
J Mol Cell Cardiol. 2021 Oct;159:120-129
pubmed: 34175302
Cell. 2016 Feb 25;164(5):999-1014
pubmed: 26875865
Nature. 1993 Sep 9;365(6442):179-81
pubmed: 8371760
Nucleic Acids Res. 2017 Mar 17;45(5):2354-2367
pubmed: 28426095
Mol Cell. 2011 Jul 8;43(1):145-55
pubmed: 21726817
Circ Res. 2018 Sep 14;123(7):773-786
pubmed: 30355081
Genome Biol. 2014;15(12):550
pubmed: 25516281
Development. 2014 Feb;141(4):878-88
pubmed: 24496624
Nat Commun. 2018 Nov 19;9(1):4877
pubmed: 30451828
Genes Dev. 1993 Jul;7(7B):1309-17
pubmed: 8330736
Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5588-93
pubmed: 23487791
Genome Biol. 2010;11(2):R14
pubmed: 20132535
Science. 2020 Jan 24;367(6476):405-411
pubmed: 31974247
Science. 2020 Sep 4;369(6508):
pubmed: 32883834
Circ Res. 2017 Jun 9;120(12):1958-1968
pubmed: 28596174
Mol Cell. 2017 Dec 21;68(6):1067-1082.e12
pubmed: 29272704
Cell Regen. 2014 Jan 24;3(1):1
pubmed: 25408880
Nat Cell Biol. 2015 Jul;17(7):856-67
pubmed: 26098572
Cell Stem Cell. 2017 Dec 7;21(6):819-833.e6
pubmed: 29220666
Curr Protoc Mol Biol. 2015 Jan 05;109:21.29.1-21.29.9
pubmed: 25559105
Nat Methods. 2013 Dec;10(12):1213-8
pubmed: 24097267
Cell. 2012 Feb 3;148(3):473-86
pubmed: 22304916
Mol Cell. 2017 Sep 21;67(6):1037-1048.e6
pubmed: 28890333
Nat Protoc. 2013 Jan;8(1):162-75
pubmed: 23257984
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Exp Mol Med. 2022 Dec;54(12):2175-2187
pubmed: 36481938
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
J Cell Biol. 1999 May 31;145(5):1049-61
pubmed: 10352021
Sci Adv. 2022 Mar 11;8(10):eabg0834
pubmed: 35275720
Nat Protoc. 2020 Jul;15(7):2247-2276
pubmed: 32561888
Cell Stem Cell. 2019 Jul 3;25(1):149-164.e9
pubmed: 31230860
Nat Methods. 2015 Jul;12(7):595-6
pubmed: 26125590
Science. 2016 Jun 3;352(6290):1216-20
pubmed: 27127239
Circ Res. 2012 Jun 22;111(1):50-5
pubmed: 22581928