دورية أكاديمية

Defining cardiac cell populations and relative cellular composition of the early fetal human heart.

التفاصيل البيبلوغرافية
العنوان: Defining cardiac cell populations and relative cellular composition of the early fetal human heart.
المؤلفون: Dewing JM; Institute for Developmental Sciences, School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., Saunders V; Institute for Developmental Sciences, School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom., O'Kelly I; Institute for Developmental Sciences, School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.; Immunocore Ltd, Abingdon, Oxford, United Kingdom., Wilson DI; Institute for Developmental Sciences, School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
المصدر: PloS one [PLoS One] 2022 Nov 30; Vol. 17 (11), pp. e0259477. Date of Electronic Publication: 2022 Nov 30 (Print Publication: 2022).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Endothelial Cells* , Fetal Heart*, Adult ; Humans ; Vimentin/genetics ; Myocytes, Cardiac ; Troponin I/genetics ; Myosin Heavy Chains/genetics
مستخلص: While the adult human heart is primarily composed of cardiomyocytes, fibroblasts, endothelial and smooth muscle cells, the cellular composition during early development remains largely unknown. Reliable identification of fetal cardiac cell types using protein markers is critical to understand cardiac development and delineate the cellular composition of the developing human heart. This is the first study to use immunohistochemistry (IHC), flow cytometry and RT-PCR analyses to investigate the expression and specificity of commonly used cardiac cell markers in the early human fetal heart (8-12 post-conception weeks). The expression of previously reported protein markers for the detection of cardiomyocytes (Myosin Heavy Chain (MHC) and cardiac troponin I (cTnI), fibroblasts (DDR2, THY1, Vimentin), endothelial cells (CD31) and smooth muscle cells (α-SMA) were assessed. Two distinct populations of cTnI positive cells were identified through flow cytometry, with MHC positive cardiomyocytes showing high cTnI expression (cTnIHigh) while MHC negative non-myocytes showed lower cTnI expression (cTnILow). cTnI expression in non-myocytes was further confirmed by IHC and RT-PCR analyses, suggesting troponins are not cardiomyocyte-specific and may play distinct roles in non-muscle cells during early development. Vimentin (VIM) was expressed in cultured ventricular fibroblast populations and flow cytometry revealed VIMHigh and VIMLow cell populations in the fetal heart. MHC positive cardiomyocytes were VIMLow whilst CD31 positive endothelial cells were VIMHigh. Using markers investigated within this study, we characterised fetal human cardiac populations and estimate that 75-80% of fetal cardiac cells are cardiomyocytes and are MHC+/cTnIHigh/VIMLow, whilst non-myocytes comprise 20-25% of total cells and are MHC-/cTnILow/VIMHigh, with CD31+ endothelial cells comprising ~9% of this population. These findings show distinct differences from those reported for adult heart.
Competing Interests: The authors have read the journal’s policy and have the following competing interests: IO is a paid employee of Immunocore. There are no patents, products in development or marketed products associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
(Copyright: © 2022 Dewing et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
References: Microsc Res Tech. 2000 Sep 15;50(6):532-40. (PMID: 10998642)
Circ Res. 2016 Feb 5;118(3):368-70. (PMID: 26846633)
J Mol Cell Cardiol. 2016 Feb;91:1-5. (PMID: 26748307)
Diabetes. 2005 May;54(5):1581-7. (PMID: 15855349)
Hypertension. 2005 Sep;46(3):614-21. (PMID: 16087782)
Nat Protoc. 2013 Jun;8(6):1204-15. (PMID: 23722259)
Cell Rep. 2019 Feb 12;26(7):1934-1950.e5. (PMID: 30759401)
Genesis. 2013 Sep;51(9):667-75. (PMID: 23775847)
Sci Rep. 2012;2:979. (PMID: 23248744)
Microcirculation. 2014 May;21(4):333-44. (PMID: 24387004)
Dev Dyn. 2004 Aug;230(4):787-94. (PMID: 15254913)
J Mol Cell Cardiol. 2007 May;42(5):991-1000. (PMID: 17395197)
Anat Rec. 1996 Oct;246(2):271-8. (PMID: 8888968)
Cardiovasc Res. 2020 Jul 1;116(8):1446-1457. (PMID: 31589297)
J Mol Cell Cardiol. 2012 Sep;53(3):323-32. (PMID: 22575762)
Microsc Microanal. 2005 Jun;11(3):260-7. (PMID: 16060979)
Circ Res. 2017 Feb 17;120(4):627-629. (PMID: 28209795)
Cell. 2015 Jun 18;161(7):1566-75. (PMID: 26073943)
FASEB J. 2006 Jun;20(8):1045-54. (PMID: 16770003)
J Exp Med. 1993 May 1;177(5):1331-42. (PMID: 7683034)
Circ Res. 2015 Jan 2;116(1):150-66. (PMID: 25552694)
J Cardiovasc Pharmacol. 2011 Apr;57(4):376-9. (PMID: 21297493)
Biochim Biophys Acta. 2016 Jul;1863(7 Pt B):1728-48. (PMID: 26524115)
J Mol Cell Cardiol. 1996 Jun;28(6):1211-25. (PMID: 8782063)
Am J Physiol Cell Physiol. 2006 Sep;291(3):C483-9. (PMID: 16571866)
PLoS One. 2013 Dec 30;8(12):e82403. (PMID: 24386094)
Am J Physiol Heart Circ Physiol. 2006 Sep;291(3):H1015-26. (PMID: 16617141)
Front Cell Dev Biol. 2021 May 12;9:645276. (PMID: 34055776)
Cell. 2010 Aug 6;142(3):375-86. (PMID: 20691899)
Am Heart J. 1980 Nov;100(5):610-6. (PMID: 6449858)
Cardiovasc Res. 2005 Jan 1;65(1):40-51. (PMID: 15621032)
Anat Rec (Hoboken). 2010 May;293(5):762-9. (PMID: 19479965)
Annu Rev Cell Dev Biol. 2012;28:719-41. (PMID: 23057748)
Circulation. 2020 Aug 4;142(5):466-482. (PMID: 32403949)
Heart Fail Rev. 2019 Jan;24(1):1-15. (PMID: 29987445)
Circ Res. 2009 Dec 4;105(12):1164-76. (PMID: 19959782)
J Mol Biol. 1988 May 20;201(2):379-91. (PMID: 3166492)
Oncotarget. 2017 Dec 4;9(1):1461-1482. (PMID: 29416706)
J Immunol. 2004 Mar 15;172(6):3850-9. (PMID: 15004192)
Am J Physiol Heart Circ Physiol. 2013 Nov 1;305(9):H1363-72. (PMID: 23997102)
Am J Physiol Heart Circ Physiol. 2007 Sep;293(3):H1883-91. (PMID: 17604329)
Eur Heart J. 1991 Apr;12(4):488-94. (PMID: 1829680)
Circ Res. 2016 Feb 5;118(3):400-9. (PMID: 26635390)
Nat Cell Biol. 2012 Dec;14(12):1251-60. (PMID: 23143399)
معلومات مُعتمدة: G1000406 United Kingdom Medical Research Council; 099175/Z/12/Z United Kingdom Wellcome Trust
المشرفين على المادة: 0 (Vimentin)
0 (Troponin I)
EC 3.6.4.1 (Myosin Heavy Chains)
تواريخ الأحداث: Date Created: 20221130 Date Completed: 20221202 Latest Revision: 20221213
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC9710754
DOI: 10.1371/journal.pone.0259477
PMID: 36449524
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0259477