Sim, Choon Boon and Phipson, Belinda and Ziemann, Mark and Rafehi, Haloom and Mills, Richard J. and Watt, Kevin I. and Abu-Bonsrah, Kwaku D. and Kalathur, Ravi K.R. and Voges, Holly K. and Dinh, Doan T. and ter Huurne, Menno and Vivien, Celine J. and Kaspi, Antony and Kaipananickal, Harikrishnan and Hidalgo, Alejandro and Delbridge, Leanne M.D. and Robker, Rebecca L. and Gregorevic, Paul and dos Remedios, Cristobal G. and Lal, Sean and Piers, Adam T. and Konstantinov, Igor E. and Elliott, David A. and El-Osta, Assam and Oshlack, Alicia and Hudson, James E. and Porrello, Enzo R. (2021) Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor. Circulation, 143 (16). pp.1614-1628. ISSN 0009-7322
Full text not available from this repository.Abstract
BACKGROUND: Despite in-depth knowledge of the molecular mechanisms controlling embryonic heart development, little is known about the signals governing postnatal maturation of the human heart. METHODS: Single-nucleus RNA sequencing of 54 140 nuclei from 9 human donors was used to profile transcriptional changes in diverse cardiac cell types during maturation from fetal stages to adulthood. Bulk RNA sequencing and the Assay for Transposase-Accessible Chromatin using sequencing were used to further validate transcriptional changes and to profile alterations in the chromatin accessibility landscape in purified cardiomyocyte nuclei from 21 human donors. Functional validation studies of sex steroids implicated in cardiac maturation were performed in human pluripotent stem cell-derived cardiac organoids and mice. RESULTS: Our data identify the progesterone receptor as a key mediator of sex-dependent transcriptional programs during cardiomyocyte maturation. Functional validation studies in human cardiac organoids and mice demonstrate that the progesterone receptor drives sex-specific metabolic programs and maturation of cardiac contractile properties. CONCLUSIONS: These data provide a blueprint for understanding human heart maturation in both sexes and reveal an important role for the progesterone receptor in human heart development.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 31 Jul 2021 05:45 |
| Last Modified: | 31 Jul 2021 05:45 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1101 |
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