Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells.
Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells.
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单细胞转录组分析揭示间充质干细胞的细胞异质性。
DOI：
10.1016/j.gpb.2022.01.005
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发表时间：
2022-02
影响因子：
9.5
通讯作者：
Wang, Qian-Fei
中科院分区：
文献类型：
--
作者：
Zhang, Chen;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
关键词：
体外扩增的间充质干细胞（MSCs）已被证明是一种异质性的细胞混合物，表现出不同的增殖、多能性和免疫调节能力。然而，间充质干细胞的确切特征在很大程度上仍然未知。通过对来自骨髓和沃顿水母的61296个MSCs进行单细胞RNA测序，我们发现了五个不同的亚群。我们绘制了这5个MSC亚群的发育轨迹，揭示了从干细胞样活性增殖细胞（APCs）到多能祖细胞的分化路径，随后分化为两条路径：1)单能前脂肪细胞或2)双能软骨前成骨细胞，后者随后分化为单能软骨前细胞。表达血管周围中胚层祖细胞标记物CSPG4/MCAM/NES的茎样APCs独特地表现出强烈的增殖和干性特征。值得注意的是，软骨前细胞亚群特异性表达免疫调节基因，并能够在体外抑制活化的CD3+ T细胞增殖，支持该群体在免疫调节中的作用。总之，我们的分析绘制了MSCs的异质性亚群，并确定了两个在自我更新和免疫调节方面具有潜在功能的亚群。我们的研究结果通过鉴定其异质细胞组成的特定功能来推进MSC的定义，通过纯化其功能亚群，允许更特异性和有效的MSC应用。
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 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 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 their heterogeneous cellular composition, allowing for more specific and effective MSC application through the purification of their functional subpopulations.
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影响因子：
7.5
作者：
Batsali AK;Pontikoglou C;Koutroulakis D;Pavlaki KI;Damianaki A;Mavroudi I;Alpantaki K;Kouvidi E;Kontakis G;Papadaki HA
通讯作者：
Papadaki HA
影响因子：
64.5
作者：
Baryawno, Ninib;Przybylski, Dariusz;Scadden, David T.
通讯作者：
Scadden, David T.
影响因子：
4
作者：
Barrett, Angela N.;Fong, Chui-Yee;Bongso, Ariff
通讯作者：
Bongso, Ariff
影响因子：
5.3
作者：
Jia, Zhaofeng;Wang, Shijin;Liu, Qisong
通讯作者：
Liu, Qisong
影响因子：
5.2
作者：
Baksh, Dolores;Yao, Raphael;Tuan, Rocky S.
通讯作者：
Tuan, Rocky S.