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TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia
BACKGROUND: Perivascular adipose-derived stem cells (PVASCs) can contribute to vascular remodeling, which are also capable of differentiating into multiple cell lineages. The present study aims to investigate the mechanism of PVASC differentiation toward smooth muscle cells (SMCs) and endothelial ce...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206642/ https://www.ncbi.nlm.nih.gov/pubmed/34150759 http://dx.doi.org/10.3389/fcell.2021.662704 |
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author | Ji, Yongli Ma, Yuankun Shen, Jian Ni, Hui Lu, Yunrui Zhang, Yuhao Ma, Hong Liu, Chang Zhao, Yiming Ding, Siyin Xiang, Meixiang Xie, Yao |
author_facet | Ji, Yongli Ma, Yuankun Shen, Jian Ni, Hui Lu, Yunrui Zhang, Yuhao Ma, Hong Liu, Chang Zhao, Yiming Ding, Siyin Xiang, Meixiang Xie, Yao |
author_sort | Ji, Yongli |
collection | PubMed |
description | BACKGROUND: Perivascular adipose-derived stem cells (PVASCs) can contribute to vascular remodeling, which are also capable of differentiating into multiple cell lineages. The present study aims to investigate the mechanism of PVASC differentiation toward smooth muscle cells (SMCs) and endothelial cells (ECs) as well as its function in neointimal hyperplasia. METHODS: Single-cell sequencing and bulk mRNA sequencing were applied for searching key genes in PVASC regarding its role in vascular remodeling. PVASCs were induced to differentiate toward SMCs and ECs in vitro, which was quantitatively evaluated using immunofluorescence, quantitative real-time PCR (QPCR), and Western blot. Lentivirus transfections were performed in PVASCs to knock down or overexpress TBX20. In vivo, PVASCs transfected with lentivirus were transplanted around the guidewire injured femoral artery. Hematoxylin–eosin (H&E) staining was performed to examine their effects on neointimal hyperplasia. RESULTS: Bulk mRNA sequencing and single-cell sequencing revealed a unique expression of TBX20 in PVASCs. TBX20 expression markedly decreased during smooth muscle differentiation while it increased during endothelial differentiation of PVASCs. TBX20 knockdown resulted in the upregulation of SMC-specific marker expression and activated Smad2/3 signaling, while inhibiting endothelial differentiation. In contrast, TBX20 overexpression repressed the differentiation of PVASCs toward smooth muscle cells but promoted endothelial differentiation in vitro. Transplantation of PVASCs transfected with TBX20 overexpression lentivirus inhibited neointimal hyperplasia in a murine femoral artery guidewire injury model. On the contrary, neointimal hyperplasia significantly increased in the TBX20 knockdown group. CONCLUSION: A subpopulation of PVASCs uniquely expressed TBX20. TBX20 could regulate SMC and EC differentiation of PVASCs in vitro. Transplantation of PVASCs after vascular injury suggested that PVASCs participated in neointimal hyperplasia via TBX20. |
format | Online Article Text |
id | pubmed-8206642 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82066422021-06-17 TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia Ji, Yongli Ma, Yuankun Shen, Jian Ni, Hui Lu, Yunrui Zhang, Yuhao Ma, Hong Liu, Chang Zhao, Yiming Ding, Siyin Xiang, Meixiang Xie, Yao Front Cell Dev Biol Cell and Developmental Biology BACKGROUND: Perivascular adipose-derived stem cells (PVASCs) can contribute to vascular remodeling, which are also capable of differentiating into multiple cell lineages. The present study aims to investigate the mechanism of PVASC differentiation toward smooth muscle cells (SMCs) and endothelial cells (ECs) as well as its function in neointimal hyperplasia. METHODS: Single-cell sequencing and bulk mRNA sequencing were applied for searching key genes in PVASC regarding its role in vascular remodeling. PVASCs were induced to differentiate toward SMCs and ECs in vitro, which was quantitatively evaluated using immunofluorescence, quantitative real-time PCR (QPCR), and Western blot. Lentivirus transfections were performed in PVASCs to knock down or overexpress TBX20. In vivo, PVASCs transfected with lentivirus were transplanted around the guidewire injured femoral artery. Hematoxylin–eosin (H&E) staining was performed to examine their effects on neointimal hyperplasia. RESULTS: Bulk mRNA sequencing and single-cell sequencing revealed a unique expression of TBX20 in PVASCs. TBX20 expression markedly decreased during smooth muscle differentiation while it increased during endothelial differentiation of PVASCs. TBX20 knockdown resulted in the upregulation of SMC-specific marker expression and activated Smad2/3 signaling, while inhibiting endothelial differentiation. In contrast, TBX20 overexpression repressed the differentiation of PVASCs toward smooth muscle cells but promoted endothelial differentiation in vitro. Transplantation of PVASCs transfected with TBX20 overexpression lentivirus inhibited neointimal hyperplasia in a murine femoral artery guidewire injury model. On the contrary, neointimal hyperplasia significantly increased in the TBX20 knockdown group. CONCLUSION: A subpopulation of PVASCs uniquely expressed TBX20. TBX20 could regulate SMC and EC differentiation of PVASCs in vitro. Transplantation of PVASCs after vascular injury suggested that PVASCs participated in neointimal hyperplasia via TBX20. Frontiers Media S.A. 2021-06-02 /pmc/articles/PMC8206642/ /pubmed/34150759 http://dx.doi.org/10.3389/fcell.2021.662704 Text en Copyright © 2021 Ji, Ma, Shen, Ni, Lu, Zhang, Ma, Liu, Zhao, Ding, Xiang and Xie. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Ji, Yongli Ma, Yuankun Shen, Jian Ni, Hui Lu, Yunrui Zhang, Yuhao Ma, Hong Liu, Chang Zhao, Yiming Ding, Siyin Xiang, Meixiang Xie, Yao TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia |
title | TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia |
title_full | TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia |
title_fullStr | TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia |
title_full_unstemmed | TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia |
title_short | TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia |
title_sort | tbx20 contributes to balancing the differentiation of perivascular adipose-derived stem cells to vascular lineages and neointimal hyperplasia |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206642/ https://www.ncbi.nlm.nih.gov/pubmed/34150759 http://dx.doi.org/10.3389/fcell.2021.662704 |
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