Deciphering transcriptome alterations in bone marrow hematopoiesis at single-cell resolution in immune thrombocytopenia.
Deciphering transcriptome alterations in bone marrow hematopoiesis at single-cell resolution in immune thrombocytopenia.
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以单细胞分辨率破译免疫性血小板减少症中骨髓造血的转录组变化
DOI：
10.1038/s41392-022-01167-9
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发表时间：
2022-10-07
影响因子：
39.3
通讯作者：
Peng, Jun
中科院分区：
文献类型：
--
作者：
Liu, Yan;Zuo, Xinyi;Chen, Peng;Hu, Xiang;Sheng, Zi;Liu, Anli;Liu, Qiang;Leng, Shaoqiu;Zhang, Xiaoyu;Li, Xin;Wang, Limei;Feng, Qi;Li, Chaoyang;Hou, Ming;Chu, Chong;Ma, Shihui;Wang, Shuwen;Peng, Jun
免疫性血小板减少症(ITP)是一种自身免疫性疾病，由自身免疫反应引起的巨核细胞功能障碍可导致血小板减少，但其潜在机制尚不清楚。在这里，我们对骨髓CD34+造血干细胞和祖细胞(HSPC)进行了单细胞转录组谱分析，以确定ITP患者巨核细胞的缺陷。ITP的HSPC的基因表达、细胞间相互作用和转录调控网络各不相同，尤其是在免疫细胞前体细胞中。差异表达基因(DEG)分析表明，ITP的巨核细胞生成受损。流式细胞仪检测证实，LIN−CD34+CD45RA−HSPC中CD9+、HES1+细胞数量减少。液体培养结果显示CD9+LIN−CD34+CD45RA−有向巨核细胞分化的趋势，但在ITP患者中未观察到这一趋势，并产生了更多的红细胞。CD9+LIN−CD34+CD45RA−−向巨核细胞分化的百分率是健康对照CD9−的3倍，而ITP患者的巨核细胞分化百分率仅为HCs的1/4，与CD9 CD9 HSPC的分化百分率相当。另外，当CD9+LIN−CD34+CD45RA−HSPC与ITP患者的Pre-B细胞共同培养时，其向巨核系的分化受到抑制。进一步分析发现，巨核细胞祖细胞(MKP)可分为7个亚群，具有不同的基因表达模式和功能。与ITP相关的DEG是MKP亚型特异性的，大多数DEG集中在具有免疫调节和血小板生成双重功能的亚群。这项研究全面剖析了缺陷的造血功能，并为ITP的发病机制提供了新的见解。
Immune thrombocytopenia (ITP) is an autoimmune disorder, in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia, although the underlying mechanisms remain unclear. Here, we performed single-cell transcriptome profiling of bone marrow CD34+ hematopoietic stem and progenitor cells (HSPCs) to determine defects in megakaryopoiesis in ITP. Gene expression, cell-cell interactions, and transcriptional regulatory networks varied in HSPCs of ITP, particularly in immune cell progenitors. Differentially expressed gene (DEG) analysis indicated that there was an impaired megakaryopoiesis of ITP. Flow cytometry confirmed that the number of CD9+ and HES1+ cells from Lin−CD34+CD45RA− HSPCs decreased in ITP. Liquid culture assays demonstrated that CD9+Lin−CD34+CD45RA− HSPCs tended to differentiate into megakaryocytes; however, this tendency was not observed in ITP patients and more erythrocytes were produced. The percentage of megakaryocytes differentiated from CD9+Lin−CD34+CD45RA− HSPCs was 3-fold higher than that of the CD9− counterparts from healthy controls (HCs), whereas, in ITP patients, the percentage decreased to only 1/4th of that in the HCs and was comparable to that from the CD9− HSPCs. Additionally, when co-cultured with pre-B cells from ITP patients, the differentiation of CD9+Lin−CD34+CD45RA− HSPCs toward the megakaryopoietic lineage was impaired. Further analysis revealed that megakaryocytic progenitors (MkP) can be divided into seven subclusters with different gene expression patterns and functions. The ITP-associated DEGs were MkP subtype-specific, with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation. This study comprehensively dissects defective hematopoiesis and provides novel insights regarding the pathogenesis of ITP.
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人类巨核细胞的细胞异质性和免疫亚群的表征
DOI：
10.1002/advs.202100921
发表时间：
2021-08
期刊：
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
影响因子：
--
作者：
Liu C;Wu D;Xia M;Li M;Sun Z;Shen B;Liu Y;Jiang E;Wang H;Su P;Shi L;Xiao Z;Zhu X;Zhou W;Wang Q;Gao X;Cheng T;Zhou J
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Li, Shuguang;Wang, Lin;Hou, Ming
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Hou, Ming
影响因子：
158.5
作者：
HOFFMAN, R;ZAKNOEN, S;PRCHAL, JT
通讯作者：
PRCHAL, JT
影响因子：
10.4
作者：
Chang, Y.;Bluteau, D.;Vainchenker, W.
通讯作者：
Vainchenker, W.
骨髓重塑支持小鼠的免疫血小板减少进展。
影响因子：
7.5
作者：
Herd, Oliver J.;Rani, Gulab Fatima;Hewitson, James P.;Hogg, Karen;Stone, Andrew P.;Cooper, Nichola;Kent, David G.;Genever, Paul G.;Hitchcock, Ian S.
通讯作者：
Hitchcock, Ian S.