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Analyses of the pericyte transcriptome in ischemic skeletal muscles
BACKGROUND: Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic t...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962292/ https://www.ncbi.nlm.nih.gov/pubmed/33726849 http://dx.doi.org/10.1186/s13287-021-02247-3 |
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author | Teng, Yuan-chi Porfírio-Sousa, Alfredo Leonardo Ribeiro, Giulia Magri Arend, Marcela Corso da Silva Meirelles, Lindolfo Chen, Elizabeth Suchi Rosa, Daniela Santoro Han, Sang Won |
author_facet | Teng, Yuan-chi Porfírio-Sousa, Alfredo Leonardo Ribeiro, Giulia Magri Arend, Marcela Corso da Silva Meirelles, Lindolfo Chen, Elizabeth Suchi Rosa, Daniela Santoro Han, Sang Won |
author_sort | Teng, Yuan-chi |
collection | PubMed |
description | BACKGROUND: Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions. METHODS: In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing. RESULTS: Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells. CONCLUSIONS: Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02247-3. |
format | Online Article Text |
id | pubmed-7962292 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79622922021-03-16 Analyses of the pericyte transcriptome in ischemic skeletal muscles Teng, Yuan-chi Porfírio-Sousa, Alfredo Leonardo Ribeiro, Giulia Magri Arend, Marcela Corso da Silva Meirelles, Lindolfo Chen, Elizabeth Suchi Rosa, Daniela Santoro Han, Sang Won Stem Cell Res Ther Research BACKGROUND: Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions. METHODS: In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing. RESULTS: Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells. CONCLUSIONS: Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13287-021-02247-3. BioMed Central 2021-03-16 /pmc/articles/PMC7962292/ /pubmed/33726849 http://dx.doi.org/10.1186/s13287-021-02247-3 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Teng, Yuan-chi Porfírio-Sousa, Alfredo Leonardo Ribeiro, Giulia Magri Arend, Marcela Corso da Silva Meirelles, Lindolfo Chen, Elizabeth Suchi Rosa, Daniela Santoro Han, Sang Won Analyses of the pericyte transcriptome in ischemic skeletal muscles |
title | Analyses of the pericyte transcriptome in ischemic skeletal muscles |
title_full | Analyses of the pericyte transcriptome in ischemic skeletal muscles |
title_fullStr | Analyses of the pericyte transcriptome in ischemic skeletal muscles |
title_full_unstemmed | Analyses of the pericyte transcriptome in ischemic skeletal muscles |
title_short | Analyses of the pericyte transcriptome in ischemic skeletal muscles |
title_sort | analyses of the pericyte transcriptome in ischemic skeletal muscles |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962292/ https://www.ncbi.nlm.nih.gov/pubmed/33726849 http://dx.doi.org/10.1186/s13287-021-02247-3 |
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