Sex-specific control of human heart maturation by the progesterone receptor

Sim, Choon Boon, Phipson, Belinda, Ziemann, Mark, Rafehi, Haloom, Mills, Richard J, Watt, Kevin I, Abu-Bonsrah, Kwaku D, Kalathur, Ravi KR, Voges, Holly K, Dinh, Doan T, ter Huurne, Menno, Vivien, Celine J, Kaspi, Antony, Kaipananickal, Harikrishnan, Hidalgo, Alejandro, Delbridge, Lea MD, Robker, Rebecca L, Gregorevic, Paul, dos Remedios, Cristobal G, Lal, Sean, Piers, Adam T, Konstantinov, Igor E, Elliott, David A, El-Osta, Assam, Oshlack, Alicia, Hudson, James E and Porrello, Enzo R 2021, Sex-specific control of human heart maturation by the progesterone receptor, Circulation, pp. 1-41, doi: 10.1161/circulationaha.120.051921.

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Title Sex-specific control of human heart maturation by the progesterone receptor
Author(s) Sim, Choon Boon
Phipson, Belinda
Ziemann, MarkORCID iD for Ziemann, Mark
Rafehi, Haloom
Mills, Richard J
Watt, Kevin I
Abu-Bonsrah, Kwaku D
Kalathur, Ravi KR
Voges, Holly K
Dinh, Doan T
ter Huurne, Menno
Vivien, Celine J
Kaspi, Antony
Kaipananickal, Harikrishnan
Hidalgo, Alejandro
Delbridge, Lea MD
Robker, Rebecca L
Gregorevic, Paul
dos Remedios, Cristobal G
Lal, Sean
Piers, Adam T
Konstantinov, Igor E
Elliott, David A
El-Osta, Assam
Oshlack, Alicia
Hudson, James E
Porrello, Enzo R
Journal name Circulation
Start page 1
End page 41
Total pages 41
Publisher American Heart Association
Place of publication Dallas, Tex.
Publication date 2021-03-08
ISSN 0009-7322
Keyword(s) Human development
chromatin accessibility
transcriptional regulation
Summary 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 (snRNA-seq) 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 (ATAC-seq) 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 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.
Language eng
DOI 10.1161/circulationaha.120.051921
Indigenous content off
Field of Research 1102 Cardiorespiratory Medicine and Haematology
1103 Clinical Sciences
1117 Public Health and Health Services
HERDC Research category C1 Refereed article in a scholarly journal
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