Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes.
Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes.
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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
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发表时间：
2021-08
期刊：
影响因子：
--
通讯作者：
Zhou J
中科院分区：
文献类型：
--
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
巨核细胞 (MK) 及其后代血小板在多种生物过程中发挥作用，包括凝血、止血、炎症、血管生成和先天免疫。然而，成年 MK 不同的发育和细胞景观仍然是个谜。在这里，通过从人类成人骨髓 (BM) 中获得 MK 的单细胞转录组分析，揭示了 MK 内的细胞异质性，并鉴定了具有高度富集的免疫相关基因的 MK 亚群。通过体外研究人类巨核细胞生成的动态单细胞转录组图景，发现MKs的免疫特征可以追溯到祖细胞阶段。此外，还鉴定出具有免疫特征的成熟 MK 的两个表面标记 CD148 和 CD48。在功能水平上，这些CD148+CD48+MKs可以在体外和体内对免疫刺激做出快速反应，表现出免疫受体和介质的高水平表达，并可能充当免疫监视细胞。这些发现揭示了人类成人 MK 的细胞异质性和一个新的免疫子集，并且应该极大地促进对 MK 在生理和病理条件下不同功能的理解。通过对来自天然骨髓的人类巨核细胞进行单细胞转录组分析，揭示了巨核细胞的异质性，发现了以CD148和CD48标记的免疫亚群，并阐明了免疫巨核细胞作为免疫监视细胞的潜在功能。
Megakaryocytes (MKs) and their progeny platelets function in a variety of biological processes including coagulation, hemostasis, inflammation, angiogenesis, and innate immunity. However, the divergent developmental and cellular landscape of adult MKs remains mysterious. Here, by deriving the single‐cell transcriptomic profiling of MKs from human adult bone marrow (BM), cellular heterogeneity within MKs is unveiled and an MK subpopulation with high enrichment of immune‐associated genes is identified. By performing the dynamic single‐cell transcriptomic landscape of human megakaryopoiesis in vitro, it is found that the immune signatures of MKs can be traced back to the progenitor stage. Furthermore, two surface markers, CD148 and CD48, are identified for mature MKs with immune characteristics. At the functional level, these CD148+CD48+ MKs can respond rapidly to immune stimuli both in vitro and in vivo, exhibit high‐level expression of immune receptors and mediators, and may function as immune‐surveillance cells. The findings uncover the cellular heterogeneity and a novel immune subset of human adult MKs and should greatly facilitate the understanding of the divergent functions of MKs under physiological and pathological conditions. By performing single‐cell transcriptomic analysis of human megakaryocytes from native bone marrow, the megakaryocyte heterogeneity is revealed, an immune subpopulation marked by CD148 and CD48 is discovered, and the potential function of immune megakaryocytes as immune‐surveillance cells is elucidated.
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DOI：
10.1083/jcb.201304054
发表时间：
2013-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Machlus KR;Italiano JE Jr
通讯作者：
Italiano JE Jr
影响因子：
20.3
作者：
Beaulieu, Lea M.;Lin, Elaine;Freedman, Jane E.
通讯作者：
Freedman, Jane E.
影响因子：
3.5
作者：
Garrett-Sinha, LA;Hou, P;Clark, MR
通讯作者：
Clark, MR
影响因子：
10.4
作者：
Paola D'Atri, Lina;Sofia Rodriguez, Camila;Schattner, Mirta
通讯作者：
Schattner, Mirta
酪氨酰-tRNA 合成酶刺激血小板生成素非依赖性造血，加速血小板减少症的恢复。
DOI：
10.1073/pnas.1807000115
发表时间：
2018-08-28
影响因子：
11.1
作者：
Kanaji T;Vo MN;Kanaji S;Zarpellon A;Shapiro R;Morodomi Y;Yuzuriha A;Eto K;Belani R;Do MH;Yang XL;Ruggeri ZM;Schimmel P
通讯作者：
Schimmel P