Journal article
Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart
Nature (London), v 523(7559), pp 226-230
09 Jul 2015
PMID: 26098368
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Although the adult mammalian heart is incapable of meaningful functional recovery following substantial cardiomyocyte loss, it is now clear that modest cardiomyocyte turnover occurs in adult mouse and human hearts, mediated primarily by proliferation of pre-existing cardiomyocytes. However, fate mapping of these cycling cardiomyocytes has not been possible thus far owing to the lack of identifiable genetic markers. In several organs, stem or progenitor cells reside in relatively hypoxic microenvironments where the stabilization of the hypoxia-inducible factor 1 alpha (Hif-1α) subunit is critical for their maintenance and function. Here we report fate mapping of hypoxic cells and their progenies by generating a transgenic mouse expressing a chimaeric protein in which the oxygen-dependent degradation (ODD) domain of Hif-1α is fused to the tamoxifen-inducible CreERT2 recombinase. In mice bearing the creERT2-ODD transgene driven by either the ubiquitous CAG promoter or the cardiomyocyte-specific α myosin heavy chain promoter, we identify a rare population of hypoxic cardiomyocytes that display characteristics of proliferative neonatal cardiomyocytes, such as smaller size, mononucleation and lower oxidative DNA damage. Notably, these hypoxic cardiomyocytes contributed widely to new cardiomyocyte formation in the adult heart. These results indicate that hypoxia signalling is an important hallmark of cycling cardiomyocytes, and suggest that hypoxia fate mapping can be a powerful tool for identifying cycling cells in adult mammals.
Metrics
Details
- Title
- Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart
- Creators
- Wataru Kimura - The University of Texas Southwestern Medical CenterFeng Xiao - The University of Texas Southwestern Medical CenterDiana C Canseco - The University of Texas Southwestern Medical CenterShalini Muralidhar - The University of Texas Southwestern Medical CenterSuWannee Thet - The University of Texas Southwestern Medical CenterHelen M Zhang - The University of Texas Southwestern Medical CenterYezan Abderrahman - The University of Texas Southwestern Medical CenterRui Chen - The University of Texas Southwestern Medical CenterJoseph A Garcia - The University of Texas Southwestern Medical CenterJohn M Shelton - The University of Texas Southwestern Medical CenterJames A Richardson - The University of Texas Southwestern Medical CenterAbdelrahman M Ashour - The University of Texas Southwestern Medical CenterAroumougame Asaithamby - The University of Texas Southwestern Medical CenterHanquan Liang - The University of Texas Southwestern Medical CenterChao Xing - The University of Texas Southwestern Medical CenterZhigang Lu - The University of Texas Southwestern Medical CenterCheng Cheng Zhang - The University of Texas Southwestern Medical CenterHesham A Sadek - The University of Texas Southwestern Medical CenterHualou Liang - School of Biomedical Engineering, Science, and Health Systems (1997-)
- Publication Details
- Nature (London), v 523(7559), pp 226-230
- Publisher
- Springer Nature
- Grant note
- I01 BX000446 / BLRD VA R01 HL108104 / NHLBI NIH HHS UL1 TR001105 / NCATS NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000357695900038
- Scopus ID
- 2-s2.0-84938069663
- Other Identifier
- 991019320610904721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology