Cross-Tissue Characterization of Heterogeneities of Mesenchymal Stem Cells and Their Differentiation Potentials

Wenhong Hou; Li Duan; Changyuan Huang; Xingfu Li; Xiao Xu; Pengfei Qin; Ni Hong; Daping Wang; Wenfei Jin

doi:10.3389/fcell.2021.781021

Cross-Tissue Characterization of Heterogeneities of Mesenchymal Stem Cells and Their Differentiation Potentials

Front Cell Dev Biol. 2021 Dec 17:9:781021. doi: 10.3389/fcell.2021.781021. eCollection 2021.

Authors

Wenhong Hou¹, Li Duan^{2

3}, Changyuan Huang^{1

4}, Xingfu Li², Xiao Xu², Pengfei Qin¹, Ni Hong¹, Daping Wang², Wenfei Jin¹

Affiliations

¹ Shenzhen Key Laboratory of Gene Regulation and Systems Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
² Department of Orthopedics, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, China.
³ Shenzhen Institute of Geriatircs, Shenzhen, China.
⁴ School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.

Abstract

Mesenchymal stem/stromal cells (MSCs) are promising cell sources for regenerative medicine and the treatment of autoimmune disorders. Comparing MSCs from different tissues at the single-cell level is fundamental for optimizing clinical applications. Here we analyzed single-cell RNA-seq data of MSCs from four tissues, namely umbilical cord, bone marrow, synovial tissue, and adipose tissue. We identified three major cell subpopulations, namely osteo-MSCs, chondro-MSCs, and adipo/myo-MSCs, across all MSC samples. MSCs from the umbilical cord exhibited the highest immunosuppression, potentially indicating it is the best immune modulator for autoimmune diseases. MSC subpopulations, with different subtypes and tissue sources, showed pronounced differences in differentiation potentials. After we compared the cell subpopulations and cell status pre-and-post chondrogenesis induction, osteogenesis induction, and adipogenesis induction, respectively, we found MSC subpopulations expanded and differentiated when their subtypes consist with induction directions, while the other subpopulations shrank. We identified the genes and transcription factors underlying each induction at the single-cell level and subpopulation level, providing better targets for improving induction efficiency.

Keywords: Mesenchymal stem cells; adipogenic differentiation; cellular differentiation; cellular heterogeneity; chondrogenic differentiation; osteogenic differentiation; single cell RNA-seq.