Analyses of the pericyte transcriptome in ischemic skeletal muscles

Abstract

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.

Single-cell RNA sequencing identifies a paracrine interaction that may drive oncogenic notch signaling in human adenoid cystic carcinoma

“… 10 We identified proliferative CAFs expressing myosatellite cell markers PAX7 14 and MYF5 15 ( Figure 1D , pink) that were present only in tumors originating in the oral cavity (ACC7, ACC21, and ACC22), consistent with the presence of submucosal muscle tissue in the oral cavity. We identified myofibroblasts ( Figure 1D , green) expressing pericyte markers CDH6 and MCAM 16 that were seen across tumors. Two other CAF clusters corresponded to inflammatory CAF subtypes.…”

Macrophages support healing of ischemic injury by transdifferentiating towards mural cells and adopting functions important for vascular support

“…Mural cell ontogeny is known to be heterogeneous and varies depending on tissue and context (Chen et al, 2016). The predominant view is that local proliferation of pericytes is induced following injury, as shown by upregulation of genes involved in mitotic cell division (Teng et al, 2021). Likewise, neointimal smooth muscle cells have been shown to undergo phenotypic switching and consequent cell proliferation in response to vascular injury (Herring et al, 2014;Nemenoff et al, 2011).…”

“…3F). Gene set enrichment analysis performed using STRING (Szklarczyk et al, 2019) with genes upregulated in cluster 2 (versus 0) yielded various GO biological process terms (referred to as GO terms) associated with mural cell functions (Teng et al, 2021) in the ischemic muscle (Fig. 4A), including blood circulation, blood vessel development, cell junction assembly, anatomical structure morphogenesis and tube development.…”

CD146 expression profile in human skin and pre-vascularized dermo-epidermal skin substitutes in vivo

“…Since CD146 has been described as a suitable marker for pericyte isolation, in particular in skeletal muscle and non-muscle tissues [10,26], and our data on human skin sections showed that among the different perivascular markers CD146 is the most ubiquitously and strongly expressed, we decided to use CD146 as marker for human dermal pericyte isolation. Isolated CD146 + pericytes were then cultured in vitro and characterized for specific marker expression (Fig.…”