Deakin University
Browse
ziemann-sexspecificcontrol-inpress-2021.pdf (4.89 MB)

Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor

Download (4.89 MB)
Version 3 2024-06-19, 01:49
Version 2 2024-06-04, 15:43
Version 1 2021-03-11, 10:11
journal contribution
posted on 2024-06-19, 01:49 authored by CB Sim, B Phipson, Mark ZiemannMark Ziemann, H Rafehi, RJ Mills, KI Watt, KD Abu-Bonsrah, RKR Kalathur, HK Voges, DT Dinh, M Ter Huurne, CJ Vivien, A Kaspi, H Kaipananickal, A Hidalgo, LMD Delbridge, RL Robker, P Gregorevic, CG Dos Remedios, S Lal, AT Piers, IE Konstantinov, DA Elliott, A El-Osta, A Oshlack, JE Hudson, ER Porrello
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.

History

Journal

Circulation

Volume

143

Pagination

1614-1628

Location

United States

Open access

  • Yes

ISSN

0009-7322

eISSN

1524-4539

Language

English

Publication classification

C1 Refereed article in a scholarly journal

Issue

16

Publisher

LIPPINCOTT WILLIAMS & WILKINS