Format

Send to

Choose Destination
Science. 2019 Mar 7. pii: eaar2038. doi: 10.1126/science.aar2038. [Epub ahead of print]

Evidence for hormonal control of heart regenerative capacity during endothermy acquisition.

Author information

1
Cardiovascular Research Institute and Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
2
Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94158, USA.
3
Department of Medicine, Division of Cardiology, University of California San Francisco, San Francisco, CA 94158, USA.
4
Department of Internal Medicine, IGFL, INRA, Univ. Lyon 1, CNRS, ENS Lyon, 69 007 France.
5
Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, RTP, NC 27709, USA.
6
Calico Life Sciences, 1170 Veterans Blvd, South San Francisco, CA 94080, USA.
7
School of Biological Sciences, The University of Adelaide, South Australia, Adelaide, Australia.
8
Department of Molecular and Cell Biology, UC Berkeley, Berkeley, CA 94708, USA.
9
Helen Wills Neuroscience Institute and Department of Bioengineering, UC Berkeley, Berkeley, CA 94708, USA.
10
Department of Biology, Bucknell University, Lewisburg, PA 17837, USA.
11
Department of Biology and UF Genetics Institute, University of Florida, Gainesville, FL, USA.
12
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
13
Department of Physiology and Pharmacology, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
14
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX 75390-8573, USA.
15
Cardiovascular Research Institute and Department of Physiology, University of California, San Francisco, San Francisco, CA 94158, USA. guo.huang@ucsf.edu.

Abstract

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 ¾-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 tradeoff for the acquisition of endothermy.

PMID:
30846611
DOI:
10.1126/science.aar2038

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center