Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1.
Multi-omics analysis of human mesenchymal stem cells shows cell aging that alters immunomodulatory activity through the downregulation of PD-L1.
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人类间充质干细胞的多组学分析显示，细胞衰老通过下调 PD-L1 来改变免疫调节活性。
DOI：
10.1038/s41467-023-39958-5
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发表时间：
2023-07-20
影响因子：
16.6
通讯作者：
Zhang, Xiaomin
中科院分区：
文献类型：
--
作者：
Gao, Yuchen;Chi, Ying;Chen, Yunfei;Wang, Wentian;Li, Huiyuan;Zheng, Wenting;Zhu, Ping;An, Jinying;Duan, Yanan;Sun, Ting;Liu, Xiaofan;Xue, Feng;Liu, Wei;Fu, Rongfeng;Han, Zhibo;Zhang, Yingchi;Yang, Renchi;Cheng, Tao;Wei, Jun;Zhang, Lei;Zhang, Xiaomin
间充质干细胞（MSC）具有强大的免疫调节活性，并已被广泛研究其治疗炎症性疾病的治疗潜力。然而，MSC的免疫抑制功能的机制尚未完全了解，阻碍了标准化MSC为基础的治疗临床应用的发展。在这项研究中，我们分析了从脂肪组织（AD），骨髓（BM），胎盘绒毛膜（PM）和脐带（UC）分离的MSC的单细胞转录组。我们的研究结果表明，骨髓间充质干细胞经历了一个渐进的衰老过程，细胞衰老状态通过下调PD-L1表达影响其免疫抑制活性。通过对单细胞转录组学和蛋白质组学数据的综合分析，我们确定GATA 2是MSC衰老和PD-L1表达的调节因子。总的来说，我们的研究结果强调了细胞衰老和PD-L1表达在调节MSC的免疫抑制功效中的作用，并涉及围产期MSC治疗在炎症性疾病中的临床应用。间充质干细胞（MSC）用于免疫抑制治疗，需要统一的来源或异质性表征。在这里，作者使用多组学来比较来自不同来源和不同年龄供体的人MSC，并显示基因表达和免疫抑制功能的差异。
Mesenchymal stem cells (MSCs) possess potent immunomodulatory activity and have been extensively investigated for their therapeutic potential in treating inflammatory disorders. However, the mechanisms underlying the immunosuppressive function of MSCs are not fully understood, hindering the development of standardized MSC-based therapies for clinical use. In this study, we profile the single-cell transcriptomes of MSCs isolated from adipose tissue (AD), bone marrow (BM), placental chorionic membrane (PM), and umbilical cord (UC). Our results demonstrate that MSCs undergo a progressive aging process and that the cellular senescence state influences their immunosuppressive activity by downregulating PD-L1 expression. Through integrated analysis of single-cell transcriptomic and proteomic data, we identify GATA2 as a regulator of MSC senescence and PD-L1 expression. Overall, our findings highlight the roles of cell aging and PD-L1 expression in modulating the immunosuppressive efficacy of MSCs and implicating perinatal MSC therapy for clinical applications in inflammatory disorders. Mesenchymal stem cells (MSC) are used for immunosuppressive therapy and a uniform source or heterogeneity characterisation is needed. Here the authors use multi-omics to compare human MSC from different sources and ages of donors and show differences in gene expression and immunosuppressive function.
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影响因子：
12.4
作者：
Chen Q;Shou P;Zheng C;Jiang M;Cao G;Yang Q;Cao J;Xie N;Velletri T;Zhang X;Xu C;Zhang L;Yang H;Hou J;Wang Y;Shi Y
通讯作者：
Shi Y
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
11.8
作者：
Higuchi-Sanabria R;Frankino PA;Paul JW 3rd;Tronnes SU;Dillin A
通讯作者：
Dillin A
影响因子：
64.8
作者：
La Manno G;Soldatov R;Zeisel A;Braun E;Hochgerner H;Petukhov V;Lidschreiber K;Kastriti ME;Lönnerberg P;Furlan A;Fan J;Borm LE;Liu Z;van Bruggen D;Guo J;He X;Barker R;Sundström E;Castelo-Branco G;Cramer P;Adameyko I;Linnarsson S;Kharchenko PV
通讯作者：
Kharchenko PV
DOI：
10.1002/stem.2509
发表时间：
2017-03
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Davies LC;Heldring N;Kadri N;Le Blanc K
通讯作者：
Le Blanc K