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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 K R; Voges, Holly K; Dinh, Doan T; Ter Huurne, Menno; Vivien, Celine J; Kaspi, Antony; Kaipananickal, Harikrishnan; Hidalgo, Alejandro; Delbridge, Leanne M D; 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.
Afiliación
  • Sim CB; Murdoch Children's Research Institute (C.B.S., B.P., K.D.A.-B., R.K.R.K., H.K.V., M.t.H., C.J.V., A.H., A.T.P., I.E.K., D.A.E., A.O., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Phipson B; Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine (C.B.S., K.D.A.-B., R.K.R.K., M.t.H., C.J.V., L.M.D.D., A.T.P., I.E.K., D.A.E., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Ziemann M; Murdoch Children's Research Institute (C.B.S., B.P., K.D.A.-B., R.K.R.K., H.K.V., M.t.H., C.J.V., A.H., A.T.P., I.E.K., D.A.E., A.O., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Rafehi H; Peter MacCallum Cancer Centre (B.P., A.O.), University of Melbourne, Victoria, Australia.
  • Mills RJ; Department of Diabetes, Central Clinical School, Alfred Centre, Monash University, Melbourne, Victoria, Australia (M.Z., H.R., A.K., H.K., A.E.-O.).
  • Watt KI; School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, Australia (M.Z.).
  • Abu-Bonsrah KD; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.Z., H.R., K.I.W., A.K., H.K., P.G., A.E.-O.).
  • Kalathur RKR; Department of Diabetes, Central Clinical School, Alfred Centre, Monash University, Melbourne, Victoria, Australia (M.Z., H.R., A.K., H.K., A.E.-O.).
  • Voges HK; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.Z., H.R., K.I.W., A.K., H.K., P.G., A.E.-O.).
  • Dinh DT; QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia (R.J.M., J.E.H.).
  • Ter Huurne M; Peter MacCallum Cancer Centre (B.P., A.O.), University of Melbourne, Victoria, Australia.
  • Vivien CJ; Centre for Muscle Research (K.I.W., P.G., E.R.P.), University of Melbourne, Victoria, Australia.
  • Kaspi A; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.Z., H.R., K.I.W., A.K., H.K., P.G., A.E.-O.).
  • Kaipananickal H; Murdoch Children's Research Institute (C.B.S., B.P., K.D.A.-B., R.K.R.K., H.K.V., M.t.H., C.J.V., A.H., A.T.P., I.E.K., D.A.E., A.O., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Hidalgo A; Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine (C.B.S., K.D.A.-B., R.K.R.K., M.t.H., C.J.V., L.M.D.D., A.T.P., I.E.K., D.A.E., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Delbridge LMD; School of Biomedical Sciences, and Department of Paediatrics (K.D.A.-B., H.K.V., A.H., I.E.K., D.A.E.), University of Melbourne, Victoria, Australia.
  • Robker RL; Murdoch Children's Research Institute (C.B.S., B.P., K.D.A.-B., R.K.R.K., H.K.V., M.t.H., C.J.V., A.H., A.T.P., I.E.K., D.A.E., A.O., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Gregorevic P; Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine (C.B.S., K.D.A.-B., R.K.R.K., M.t.H., C.J.V., L.M.D.D., A.T.P., I.E.K., D.A.E., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Dos Remedios CG; Murdoch Children's Research Institute (C.B.S., B.P., K.D.A.-B., R.K.R.K., H.K.V., M.t.H., C.J.V., A.H., A.T.P., I.E.K., D.A.E., A.O., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Lal S; School of Biomedical Sciences, and Department of Paediatrics (K.D.A.-B., H.K.V., A.H., I.E.K., D.A.E.), University of Melbourne, Victoria, Australia.
  • Piers AT; Robinson Research Institute, The University of Adelaide, South Australia, Australia (D.T.D., R.L.R.).
  • Konstantinov IE; Murdoch Children's Research Institute (C.B.S., B.P., K.D.A.-B., R.K.R.K., H.K.V., M.t.H., C.J.V., A.H., A.T.P., I.E.K., D.A.E., A.O., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Elliott DA; Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine (C.B.S., K.D.A.-B., R.K.R.K., M.t.H., C.J.V., L.M.D.D., A.T.P., I.E.K., D.A.E., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • El-Osta A; Murdoch Children's Research Institute (C.B.S., B.P., K.D.A.-B., R.K.R.K., H.K.V., M.t.H., C.J.V., A.H., A.T.P., I.E.K., D.A.E., A.O., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Oshlack A; Melbourne Centre for Cardiovascular Genomics and Regenerative Medicine (C.B.S., K.D.A.-B., R.K.R.K., M.t.H., C.J.V., L.M.D.D., A.T.P., I.E.K., D.A.E., E.R.P.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  • Hudson JE; Department of Diabetes, Central Clinical School, Alfred Centre, Monash University, Melbourne, Victoria, Australia (M.Z., H.R., A.K., H.K., A.E.-O.).
  • Porrello ER; Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.Z., H.R., K.I.W., A.K., H.K., P.G., A.E.-O.).
Circulation ; 143(16): 1614-1628, 2021 04 20.
Article en En | MEDLINE | ID: mdl-33682422
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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores de Progesterona / Corazón Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Circulation Año: 2021 Tipo del documento: Article País de afiliación: Australia
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Receptores de Progesterona / Corazón Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: Circulation Año: 2021 Tipo del documento: Article País de afiliación: Australia