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Sim CB, Phipson B, Ziemann M, et al. Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor. Circulation. 2021;143(16):1614-1628doi: 10.1161/CIRCULATIONAHA.120.051921.
Sim, C. B., Phipson, B., Ziemann, M., Rafehi, H., Mills, R. J., Watt, K. I., Abu-Bonsrah, K. D., Kalathur, R. K. R., Voges, H. K., Dinh, D. T., Ter Huurne, M., Vivien, C. J., Kaspi, A., Kaipananickal, H., Hidalgo, A., Delbridge, L. M. D., Robker, R. L., Gregorevic, P., Dos Remedios, C. G., Lal, S., Piers, A. T., Konstantinov, I. E., Elliott, D. A., El-Osta, A., Oshlack, A., Hudson, J. E., & Porrello, E. R. (2021). Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor. Circulation, 143(16), 1614-1628. https://doi.org/10.1161/CIRCULATIONAHA.120.051921
Sim, Choon Boon, et al. "Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor." Circulation vol. 143,16 (2021): 1614-1628. doi: https://doi.org/10.1161/CIRCULATIONAHA.120.051921
Sim CB, Phipson B, Ziemann M, Rafehi H, Mills RJ, Watt KI, Abu-Bonsrah KD, Kalathur RKR, Voges HK, Dinh DT, Ter Huurne M, Vivien CJ, Kaspi A, Kaipananickal H, Hidalgo A, Delbridge LMD, Robker RL, Gregorevic P, Dos Remedios CG, Lal S, Piers AT, Konstantinov IE, Elliott DA, El-Osta A, Oshlack A, Hudson JE, Porrello ER. Sex-Specific Control of Human Heart Maturation by the Progesterone Receptor. Circulation. 2021 Apr 20;143(16):1614-1628. doi: 10.1161/CIRCULATIONAHA.120.051921. Epub 2021 Mar 08. PMID: 33682422; PMCID: PMC8055196.
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Circulation. 2021 Apr 20;143(16):1614-1628. doi: 10.1161/CIRCULATIONAHA.120.051921. Epub 2021 Mar 08.

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

Circulation

Choon Boon Sim, Belinda Phipson, Mark Ziemann, Haloom Rafehi, Richard J Mills, Kevin I Watt, Kwaku D Abu-Bonsrah, Ravi K R Kalathur, Holly K Voges, Doan T Dinh, Menno Ter Huurne, Celine J Vivien, Antony Kaspi, Harikrishnan Kaipananickal, Alejandro Hidalgo, Leanne M D Delbridge, Rebecca L Robker, Paul Gregorevic, Cristobal G Dos Remedios, Sean Lal, Adam T Piers, Igor E Konstantinov, David A Elliott, Assam El-Osta, Alicia Oshlack, James E Hudson, Enzo R Porrello

Affiliations

  1. 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.
  2. 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.
  3. Peter MacCallum Cancer Centre (B.P., A.O.), University of Melbourne, Victoria, Australia.
  4. Department of Diabetes, Central Clinical School, Alfred Centre, Monash University, Melbourne, Victoria, Australia (M.Z., H.R., A.K., H.K., A.E.-O.).
  5. School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, Australia (M.Z.).
  6. Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia (M.Z., H.R., K.I.W., A.K., H.K., P.G., A.E.-O.).
  7. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia (R.J.M., J.E.H.).
  8. Centre for Muscle Research (K.I.W., P.G., E.R.P.), University of Melbourne, Victoria, Australia.
  9. 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.
  10. Robinson Research Institute, The University of Adelaide, South Australia, Australia (D.T.D., R.L.R.).
  11. Department of Anatomy and Physiology (K.I.W., L.M.D.D., P.G., E.R.P.), University of Melbourne, Victoria, Australia.
  12. School of Medical Sciences, The University of Sydney, New South Wales, Australia (C.G.d.R., S.L.).
  13. Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia (C.G.d.R.).
  14. Department of Cardiac Surgery (I.E.K.), The Royal Children's Hospital, Melbourne, Victoria, Australia.
  15. Hong Kong Institute of Diabetes and Obesity, Prince of Wales Hospital, Li Ka Shing Institute of Health Sciences, and The Chinese University of Hong Kong, China (A.E.-O.).
  16. Centre for Cardiac and Vascular Biology, School of Biomedical Sciences, The University of Queensland, Brisbane, Australia (J.E.H., E.R.P.).

PMID: 33682422 PMCID: PMC8055196 DOI: 10.1161/CIRCULATIONAHA.120.051921

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.

Keywords: chromatin; hormone; human development; progesterone; sexual maturation; transcription factor

References

  1. J Biol Chem. 1984 May 25;259(10):6437-46 - PubMed
  2. Fertil Steril. 2004 Aug;82(2):430-6 - PubMed
  3. Science. 2019 Jul 19;365(6450): - PubMed
  4. Genome Res. 2003 Nov;13(11):2498-504 - PubMed
  5. Circ Cardiovasc Qual Outcomes. 2018 Feb;11(2):e004437 - PubMed
  6. J Appl Physiol (1985). 2012 May;112(9):1564-75 - PubMed
  7. Bioinformatics. 2009 Jul 15;25(14):1754-60 - PubMed
  8. Card Fail Rev. 2017 Apr;3(1):7-11 - PubMed
  9. Nat Commun. 2018 Jan 26;9(1):391 - PubMed
  10. Development. 2017 Mar 15;144(6):1118-1127 - PubMed
  11. Bioinformatics. 2014 Apr 1;30(7):923-30 - PubMed
  12. Nat Commun. 2018 Apr 10;9(1):1373 - PubMed
  13. Circulation. 2017 Sep 19;136(12):1123-1139 - PubMed
  14. Nucleic Acids Res. 2016 Jul 8;44(W1):W160-5 - PubMed
  15. BMC Genomics. 2020 Jun 29;21(1):447 - PubMed
  16. Gigascience. 2018 Jul 1;7(7): - PubMed
  17. Circ Res. 2020 Apr 10;126(8):1086-1106 - PubMed
  18. BMC Bioinformatics. 2014 Aug 29;15:293 - PubMed
  19. J Vis Exp. 2012 Jul 10;(65): - PubMed
  20. Circulation. 2020 Oct 13;142(15):1448-1463 - PubMed
  21. Cell Stem Cell. 2019 Jun 6;24(6):895-907.e6 - PubMed
  22. Nat Commun. 2014 Oct 22;5:5288 - PubMed
  23. Cardiovasc Res. 2020 Sep 17;: - PubMed
  24. BMC Bioinformatics. 2014 Jun 12;15:182 - PubMed
  25. Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1446-51 - PubMed
  26. Dev Cell. 2016 Nov 21;39(4):491-507 - PubMed
  27. Genome Biol. 2019 Dec 23;20(1):296 - PubMed
  28. Nucleic Acids Res. 2015 Apr 20;43(7):e47 - PubMed
  29. Development. 2020 Nov 30;147(22): - PubMed
  30. Trends Endocrinol Metab. 2018 Jul;29(7):481-491 - PubMed
  31. Genes Dev. 2018 Oct 1;32(19-20):1344-1357 - PubMed
  32. Dev Cell. 2016 Nov 21;39(4):480-490 - PubMed
  33. Ann Appl Stat. 2016 Jun;10(2):946-963 - PubMed
  34. Physiol Rev. 2017 Jan;97(1):1-37 - PubMed
  35. Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):E8372-E8381 - PubMed
  36. Nat Methods. 2011 Oct 23;8(12):1037-40 - PubMed
  37. Circ Heart Fail. 2012 Jul 1;5(4):523-34 - PubMed
  38. Nat Biotechnol. 2018 Jun;36(5):411-420 - PubMed
  39. NPJ Regen Med. 2016 Jul 28;1:16012 - PubMed
  40. Bioinformatics. 2010 Jan 1;26(1):139-40 - PubMed
  41. Nat Commun. 2020 Jun 2;11(1):2843 - PubMed
  42. Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50 - PubMed
  43. Genome Biol. 2008;9(9):R137 - PubMed
  44. Genome Biol. 2014 Feb 03;15(2):R29 - PubMed
  45. Adv Physiol Educ. 2007 Mar;31(1):26-33 - PubMed
  46. Cell. 2019 Jun 27;178(1):242-260.e29 - PubMed
  47. Nat Rev Genet. 2019 May;20(5):257-272 - PubMed
  48. Circulation. 2020 Aug 4;142(5):466-482 - PubMed
  49. Nature. 2020 Dec;588(7838):466-472 - PubMed
  50. Mol Cell. 2010 May 28;38(4):576-89 - PubMed
  51. Bioinformatics. 2013 Jan 1;29(1):15-21 - PubMed
  52. Aging Male. 2004 Sep;7(3):236-57 - PubMed
  53. Sci Rep. 2019 Jun 27;9(1):9354 - PubMed
  54. Nat Biotechnol. 2011 Jan;29(1):24-6 - PubMed
  55. APL Bioeng. 2018 Mar 20;2(2):026102 - PubMed
  56. Clin Chem Lab Med. 2006;44(7):883-7 - PubMed
  57. Cell Rep. 2019 Feb 12;26(7):1934-1950.e5 - PubMed
  58. Cell. 2019 Jun 13;177(7):1888-1902.e21 - PubMed
  59. Bioinformatics. 2009 Mar 15;25(6):765-71 - PubMed
  60. Cardiovasc Res. 2013 Dec 1;100(3):402-10 - PubMed
  61. Stem Cell Res. 2019 Jan;34:101380 - PubMed
  62. Science. 2018 Mar 9;359(6380):1177-1181 - PubMed
  63. Bioinformatics. 2009 Aug 15;25(16):2078-9 - PubMed
  64. Bioinformatics. 2015 Sep 1;31(17):2912-4 - PubMed
  65. Nat Commun. 2020 Nov 30;11(1):6077 - PubMed
  66. Nat Commun. 2020 Aug 26;11(1):4267 - PubMed
  67. Nucleic Acids Res. 2009 Jul;37(Web Server issue):W305-11 - PubMed
  68. Lancet Child Adolesc Health. 2020 Mar;4(3):168-169 - PubMed
  69. Nucleic Acids Res. 2012 Sep 1;40(17):e133 - PubMed

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