Analyses of the pericyte transcriptome in ischemic skeletal muscles

Author(s)

Teng, Yuan-chi ^[1] ; Porfirio-Sousa, Alfredo Leonardo ^[2] ; Ribeiro, Giulia Magri ^[2] ; Arend, Marcela Corso ^[1] ; Meirelles, Lindolfo da Silva ^[3] ; Chen, Elizabeth Suchi ^[4] ; Rosa, Daniela Santoro ^[5] ; Han, Sang Won ^{[1, 6]}

Affiliation

^[1] Univ Fed Sao Paulo, Escola Paulista Med, Dept Biophys, Rua Mirassol 207, BR-04044010 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Dept Zool, Sao Paulo - Brazil

^[3] Univ Luterana Brasil, Lab Stem Cells & Tissue Engn, Canoas - Brazil

^[4] Univ Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo - Brazil

^[5] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, Interdisciplinary Ctr Gene, Sao Paulo - Brazil

• Document type: Journal article
• Source: STEM CELL RESEARCH & THERAPY; v. 12, n. 1 MAR 16 2021.
• Web of Science Citations: 0

Abstract

BackgroundPeripheral 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.MethodsIn 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.ResultsIschemia 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.ConclusionsOur 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. (AU)

• FAPESP's process: 17/17588-1 - Forced expression effect of GM-CSF and M-CSF genes in ischemic skeletal muscle
• Grantee: Yuan-Chi Teng
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia
• Grantee: Sang Won Han
• Support type: Research Projects - Thematic Grants