RT Journal Article
SR Electronic
T1 Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.11.24.469676
DO 10.1101/2021.11.24.469676
A1 Chen Zhang
A1 Xueshuai Han
A1 Jingkun Liu
A1 Lei Chen
A1 Ying Lei
A1 Kunying Chen
A1 Jia Si
A1 Tian-yi Wang
A1 Hui Zhou
A1 Xiaoyun Zhao
A1 Xiaohui Zhang
A1 Yihua An
A1 Yueying Li
A1 Qian-fei Wang
YR 2021
UL http://biorxiv.org/content/early/2021/11/24/2021.11.24.469676.abstract
AB Ex vivo-expanded mesenchymal stem cells (MSCs) have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative, multipotential, and immunomodulatory capacities. However, the exact characteristics of MSCs remain largely unknown. By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton’s jelly, we revealed five distinct subpopulations. The developmental trajectory of these five MSC subpopulations were mapped, revealing a differentiation path from stem-like active proliferative cells (APCs) to multipotent progenitor cells, followed by the branching into two paths – adipogenesis or osteochondrogenesis – and subsequent differentiation into unipotent prechondrocytes. The stem-like APCs, expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES, uniquely exhibited strong proliferation and stemness signatures. Remarkably, the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3+ T cell proliferation in vitro, supporting the role of this population in immunoregulation. In summary, our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation. Our findings advance the definition of MSCs by identifying the specific functions of its heterogeneous cellular composition, allowing for more specific and effective MSC application through the purification of its functional subpopulations.Competing Interest StatementThe authors have declared no competing interest.