Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells
- Author:
Zhang CHEN
1
;
Han XUESHUAI
;
Liu JINGKUN
;
Chen LEI
;
Lei YING
;
Chen KUNYING
;
Si JIA
;
Wang TIAN-YI
;
Zhou HUI
;
Zhao XIAOYUN
;
Zhang XIAOHUI
;
An YIHUA
;
Li YUEYING
;
Wang QIAN-FEI
Author Information
1. CAS Key Laboratory of Genomic and Precision Medicine,Collaborative Innovation Center of Genetics and Development,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China;China National Center for Bioinformation,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;Department of Medical Experimental Center,Qilu Hospital(Qingdao),Cheeloo College of
- Keywords:
Mesenchymal stem cell;
Single-cell RNA sequencing;
Heterogeneity;
Lineage trajectory;
Immune regulation
- From:
Genomics, Proteomics & Bioinformatics
2022;20(1):70-86
- CountryChina
- Language:Chinese
-
Abstract:
Ex vivo-expanded mesenchymal stem cells(MSCs)have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative,multipotential,and immunomodu-latory 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 was mapped,revealing a differentiation path from stem-like active proliferative cells(APCs)to multipotent progenitor cells,followed by branching into two paths:1)unipotent preadipocytes or 2)bipotent prechondro-osteoblasts that were subsequently differentiated into unipotent prechondro-cytes.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 sup-press 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 their heteroge-neous cellular composition,allowing for more specific and effective MSC application through the purification of their functional subpopulations.
