Evidence for hormonal control of heart regenerative capacity during endothermy acquisition
Kentaro Hirose
(1, 2)
,
Alexander Payumo
(1, 2)
,
Stephen Cutie
(1, 2)
,
Alison Hoang
(1, 2)
,
Hao Zhang
(3)
,
Romain Guyot
(4)
,
Dominic Lunn
(1, 2)
,
Rachel Bigley
(1, 2)
,
Hongyao Yu
(5)
,
Jiajia Wang
(5)
,
Megan Smith
(6)
,
Ellen Gillett
(7)
,
Sandra Muroy
(8)
,
Tobias Schmid
(9)
,
Emily Wilson
(3)
,
Kenneth Field
(10)
,
Deeann Reeder
(10)
,
Malcom Maden
(11)
,
Michael Yartsev
(9)
,
Michael Wolfgang
(12)
,
Frank Grützner
(7)
,
Thomas Scanlan
(13)
,
Luke Szweda
(14)
,
Rochelle Buffenstein
(6)
,
Guang Hu
(5)
,
Frederic Flamant
(4)
,
Jeffrey Olgin
(1, 3)
,
Guo Huang
(1, 2)
1
Departments of Medicine and Physiology, Cardiovascular Research Institute
2 Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research
3 Department of Medicine
4 IGFL - Institut de Génomique Fonctionnelle de Lyon
5 Epigenetics and Stem Cell Biology Laboratory
6 Calico Life Sciences
7 School of Biological Sciences
8 Department of Molecular and Cell Biology
9 Helen Wills Neuroscience Institute and Department of Bioengineering
10 Department of Biology
11 Department of Biology and UF Genetics Institute
12 Department of Biological Chemistry
13 Department of Physiology and Pharmacology
14 Division of Cardiology
2 Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research
3 Department of Medicine
4 IGFL - Institut de Génomique Fonctionnelle de Lyon
5 Epigenetics and Stem Cell Biology Laboratory
6 Calico Life Sciences
7 School of Biological Sciences
8 Department of Molecular and Cell Biology
9 Helen Wills Neuroscience Institute and Department of Bioengineering
10 Department of Biology
11 Department of Biology and UF Genetics Institute
12 Department of Biological Chemistry
13 Department of Physiology and Pharmacology
14 Division of Cardiology
Romain Guyot
- Fonction : Auteur
- PersonId : 801032
- ORCID : 0000-0002-7016-7485
- IdRef : 224213946
Frederic Flamant
- Fonction : Auteur
- PersonId : 747363
- IdHAL : frederic-flamant
- ORCID : 0000-0002-3360-2345
- IdRef : 031091261
Résumé
Tissue regenerative potential displays striking divergence across phylogeny and ontogeny, but the underlying mechanisms remain enigmatic. Loss of mammalian cardiac regenerative potential correlates with cardiomyocyte cell-cycle arrest and polyploidization as well as the development of postnatal endothermy. We reveal that diploid cardiomyocyte abundance across 41 species conforms to Kleiber's law-the 3/4 -power law scaling of metabolism with bodyweight-and inversely correlates with standard metabolic rate, body temperature, and serum thyroxine level. Inactivation of thyroid hormone signaling reduces mouse cardiomyocyte polyploidization, delays cell-cycle exit, and retains cardiac regenerative potential in adults. Conversely, exogenous thyroid hormones inhibit zebrafish heart regeneration. Thus, our findings suggest that loss of heart regenerative capacity in adult mammals is triggered by increasing thyroid hormones and may be a trade-off for the acquisition of endothermy.