Defining cardiac cell populations and relative cellular composition of the early fetal human heart
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..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
PloS one - 17(2022), 11 vom: 13., Seite e0259477 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Dewing, Jennifer M [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
EC 3.6.4.1 |
|---|
| Anmerkungen: |
Date Completed 02.12.2022 Date Revised 13.12.2022 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.pone.0259477 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM349622191 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM349622191 | ||
| 003 | DE-627 | ||
| 005 | 20231226043052.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.pone.0259477 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1165.xml |
| 035 | |a (DE-627)NLM349622191 | ||
| 035 | |a (NLM)36449524 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Dewing, Jennifer M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Defining cardiac cell populations and relative cellular composition of the early fetal human heart |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 02.12.2022 | ||
| 500 | |a Date Revised 13.12.2022 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Vimentin |2 NLM | |
| 650 | 7 | |a Troponin I |2 NLM | |
| 650 | 7 | |a Myosin Heavy Chains |2 NLM | |
| 650 | 7 | |a EC 3.6.4.1 |2 NLM | |
| 700 | 1 | |a Saunders, Vinay |e verfasserin |4 aut | |
| 700 | 1 | |a O'Kelly, Ita |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, David I |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PloS one |d 2006 |g 17(2022), 11 vom: 13., Seite e0259477 |w (DE-627)NLM167327399 |x 1932-6203 |7 nnns |
| 773 | 1 | 8 | |g volume:17 |g year:2022 |g number:11 |g day:13 |g pages:e0259477 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.pone.0259477 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 17 |j 2022 |e 11 |b 13 |h e0259477 | ||