Redifferentiated cardiomyocytes retain residual dedifferentiation signatures and are protected against ischemic injury.
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Apr 2023
Apr 2023
Historique:
medline:
17
11
2023
pubmed:
17
11
2023
entrez:
17
11
2023
Statut:
ppublish
Résumé
Cardiomyocyte proliferation and dedifferentiation have fueled the field of regenerative cardiology in recent years, whereas the reverse process of redifferentiation remains largely unexplored. Redifferentiation is characterized by the restoration of function lost during dedifferentiation. Previously, we showed that ERBB2-mediated heart regeneration has these two distinct phases: transient dedifferentiation and redifferentiation. Here we survey the temporal transcriptomic and proteomic landscape of dedifferentiation-redifferentiation in adult mouse hearts and reveal that well-characterized dedifferentiation features largely return to normal, although elements of residual dedifferentiation remain, even after the contractile function is restored. These hearts appear rejuvenated and show robust resistance to ischemic injury, even 5 months after redifferentiation initiation. Cardiomyocyte redifferentiation is driven by negative feedback signaling and requires LATS1/2 Hippo pathway activity. Our data reveal the importance of cardiomyocyte redifferentiation in functional restoration during regeneration but also protection against future insult, in what could lead to a potential prophylactic treatment against ischemic heart disease for at-risk patients.
Identifiants
pubmed: 37974970
doi: 10.1038/s44161-023-00250-w
pmc: PMC10653068
mid: NIHMS1920967
doi:
Types de publication
Journal Article
Langues
eng
Pagination
383-398Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM007739
Pays : United States
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing interests.
Références
Onco Targets Ther. 2018 Nov 02;11:7795-7803
pubmed: 30464527
Circulation. 2017 Sep 19;136(12):1123-1139
pubmed: 28733351
Circulation. 2016 Mar 15;133(11):1081-92
pubmed: 26841808
Circulation. 2022 Apr 26;145(17):1339-1355
pubmed: 35061545
Genome Biol. 2014;15(12):550
pubmed: 25516281
Science. 2011 Apr 22;332(6028):458-61
pubmed: 21512031
J Clin Invest. 1997 Jul 1;100(1):169-79
pubmed: 9202069
Nat Metab. 2020 Feb;2(2):167-178
pubmed: 32617517
Development. 2013 Dec;140(23):4683-90
pubmed: 24255096
Bioinformatics. 2015 Jan 15;31(2):166-9
pubmed: 25260700
Cell. 2018 Mar 22;173(1):104-116.e12
pubmed: 29502971
J Biol Chem. 2008 Nov 7;283(45):31246-55
pubmed: 18753132
Sci Rep. 2017 Oct 10;7(1):12879
pubmed: 29018280
Science. 2017 Jun 9;356(6342):1035-1039
pubmed: 28596337
Science. 2002 Dec 13;298(5601):2188-90
pubmed: 12481136
Sci Rep. 2020 Dec 14;10(1):21918
pubmed: 33318551
Circulation. 2004 Mar 2;109(8):1048-55
pubmed: 14967725
Sci Transl Med. 2021 Jun 30;13(600):
pubmed: 34193613
Basic Res Cardiol. 2013 Jan;108(1):309
pubmed: 23184389
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
Circ Res. 2014 Jul 18;115(3):354-63
pubmed: 24833660
Adv Med Sci. 2017 Sep;62(2):307-316
pubmed: 28511069
Elife. 2015 Apr 01;4:
pubmed: 25830562
Circ Res. 1996 Oct;79(4):691-7
pubmed: 8831492
J Clin Invest. 2017 Feb 1;127(2):569-582
pubmed: 28067668
Compr Physiol. 2015 Sep 20;5(4):1877-909
pubmed: 26426470
Int J Mol Sci. 2021 Apr 23;22(9):
pubmed: 33922534
PLoS Biol. 2013 Jul;11(7):e1001613
pubmed: 23935448
Nature. 2016 May 25;534(7605):119-23
pubmed: 27251288
J Vis Exp. 2016 Dec 2;(118):
pubmed: 28060289
J Proteome Res. 2015 Apr 3;14(4):1979-86
pubmed: 25780947
Cell Stem Cell. 2020 Jan 2;26(1):7-16
pubmed: 31901252
Elife. 2019 Dec 23;8:
pubmed: 31868166
Cell Cycle. 2005 Dec;4(12):1703-5
pubmed: 16258284
Nature. 2017 Jan 12;541(7636):222-227
pubmed: 27798600
NPJ Regen Med. 2016 Jul 28;1:16012
pubmed: 29302337
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Cell. 2016 Dec 15;167(7):1719-1733.e12
pubmed: 27984723
Cell Rep. 2019 Jul 23;28(4):966-978.e4
pubmed: 31340157
Nature. 2020 Dec;588(7839):705-711
pubmed: 33299187
Science. 2021 Sep 24;373(6562):1537-1540
pubmed: 34554778
Nature. 2013 May 9;497(7448):249-253
pubmed: 23594737
Circ Res. 2015 Feb 27;116(5):804-15
pubmed: 25477501
Gynecol Endocrinol. 2014 Aug;30(8):600-4
pubmed: 24811094
Development. 2018 Mar 6;145(5):
pubmed: 29444893
J Biol Chem. 2010 May 14;285(20):14861-14870
pubmed: 20335174
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Cell Res. 2014 Sep;24(9):1091-107
pubmed: 25124925
Nat Commun. 2021 May 25;12(1):3100
pubmed: 34035288
Cold Spring Harb Perspect Med. 2012 May;2(5):a006627
pubmed: 22553494
Cell. 2014 Apr 24;157(3):565-79
pubmed: 24766806
Dev Cell. 2019 Mar 25;48(6):765-779.e7
pubmed: 30773489
Front Cell Dev Biol. 2017 May 05;5:50
pubmed: 28529939
Nat Biotechnol. 2015 Jul;33(7):750-4
pubmed: 26098449
J Biol Chem. 2005 Dec 30;280(52):42785-93
pubmed: 16260776
Nat Cell Biol. 2015 May;17(5):627-38
pubmed: 25848746
Carcinogenesis. 2010 Apr;31(4):577-86
pubmed: 20097731
J Cardiovasc Dev Dis. 2021 May 05;8(5):
pubmed: 34063001
Circulation. 1997 Nov 18;96(10):3579-86
pubmed: 9396458
Anat Rec (Hoboken). 2019 Jan;302(1):93-100
pubmed: 30565418
Am J Pathol. 2009 Aug;175(2):867-81
pubmed: 19608870
Nat Cell Biol. 2020 Nov;22(11):1346-1356
pubmed: 33046882
Plant Direct. 2019 Mar 20;3(3):e00127
pubmed: 31245770
FEBS J. 2020 Feb;287(3):417-438
pubmed: 31743572
Nature. 2019 May;569(7756):418-422
pubmed: 31068698
Nucleic Acids Res. 2021 Jan 8;49(D1):D394-D403
pubmed: 33290554
Nucleic Acids Res. 2022 Jan 7;50(D1):D543-D552
pubmed: 34723319
PLoS One. 2011 Apr 12;6(4):e18503
pubmed: 21533269
Basic Res Cardiol. 2017 May;112(3):27
pubmed: 28364353
Cell Stem Cell. 2023 Jan 5;30(1):96-111.e6
pubmed: 36516837
Nature. 2017 Oct 12;550(7675):260-264
pubmed: 28976966
Inflamm Intest Dis. 2019 Oct;4(4):161-173
pubmed: 31768389
Cell. 2009 Feb 6;136(3):535-50
pubmed: 19203586
Circulation. 2020 Sep;142(9):913-916
pubmed: 32866067
Cell Res. 2021 Apr;31(4):450-462
pubmed: 32973339
Microvasc Res. 2007 Sep-Nov;74(2-3):85-9
pubmed: 17602710
Lab Anim. 2020 Jun;54(3):213-224
pubmed: 31510859
Cell Rep. 2018 Feb 27;22(9):2469-2481
pubmed: 29490281
Sci Signal. 2015 May 05;8(375):ra41
pubmed: 25943351