Abstract
Umbilical cord mesenchymal stem cells (UC-MSCs) have certain advantages over other MSCs and about 300 clinical trials have been registered using UC-MSCs to treat diseases such as osteoarthritis, autoimmune diseases, and degenerative disorders, yet, only limited success has been achieved. One reason is that in vitro expanded UC-MSCs show tremendous heterogeneity and their relationship to in vivo UC-MSCs remains unknown. Here, we investigated freshly isolated, uncultured UC-MSCs by single-cell RNA sequencing (scRNA-seq) and found two populations of UC-MSCs. Although UC-MSCs share many expressed genes and may have the same origin, they can be clearly separated based on differentially expressed genes including CD73 and other markers. Moreover, group 1 MSCs are enriched in expression of genes in immune response/regulatory activities, muscle cell proliferation and differentiation, stemness, and oxidative stress while group 2 MSCs are enriched with gene expression in extracellular matrix production, osteoblast and chondrocytes differentiation, and bone and cartilage growth. These findings suggest that UC-MSCs should be separated right after isolation and individually expanded in vitro to treat different diseases.
Highlights
Umbilical cord mesenchymal stem cells (UC-Mesenchymal stem/stromal cells (MSC)) have certain advantages over other MSCs and about 300 clinical trials have been registered using UC-MSCs to treat diseases such as osteoarthritis, autoimmune diseases, and degenerative disorders, yet, only limited success has been achieved
Letter Mesenchymal stem/stromal cells (MSCs) are a group of cells that can adhere to plastic surface and proliferate, express CD73, CD90, and CD105 but not CD34, CD45, CD11b, or HLA Class II, and can differentiate into osteoblast, chondrocyte, and adipocyte in vitro [1, 2]
Previous studies have analyzed cultured UC-MSCs with scRNA-seq and found that UCMSCs could be divided into 11 subgroups [7], which showed differences in expression of genes encoding extracellular matrix (ECM), protein process, and cell
Summary
GLI1 f MSC_1 KEGG TNF signaling pathway IL-17 signaling pathway Toll-like receptor signaling pathway TGF-beta signaling pathway Kaposi sarcoma-associated herpesvirus infection Osteoclast differentiation Rheumatoid arthritis Viral protein interaction with cytokine and cytokine receptor. Chagas disease (American trypanosomiasis) Human T-cell leukemia virus 1 infection NOD-like receptor signaling pathway Leishmaniasis FoxO signaling pathway Fluid shear stress and atherosclerosis. MSC_1 GO regulation of smooth muscle cell proliferation smooth muscle cell proliferation muscle cell proliferation epithelial cell proliferation response to ketone response to mechanical stimulus myeloid cell differentiation response to reactive oxygen species response to oxidative stress cellular response to interleukin-1 response to nutrient levels cellular response to extracellular stimulus response to acid chemical positive regulation of smooth muscle cell proliferation response to interleukin-1 positive regulation of inflammatory response response to radiation fat cell differentiation regulation of inflammatory response positive regulation of vasculature development
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