Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes,Advanced Science

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Characterization of Cellular Heterogeneity and an Immune Subpopulation of Human Megakaryocytes
Advanced Science ( IF 14.3 ) Pub Date : 2021-05-26 , DOI: 10.1002/advs.202100921
Cuicui Liu _{1,

2} , Dan Wu _{1,

2} , Meijuan Xia _{1,

2} , Minmin Li _{1,

2} , Zhiqiang Sun _{1,

2} , Biao Shen _{1,

2} , Yiying Liu _{1,

2} , Erlie Jiang _{1,

2} , Hongtao Wang _{1,

2} , Pei Su _{1,

2} , Lihong Shi _{1,

2} , Zhijian Xiao _{1,

2} , Xiaofan Zhu _{1,

2} , Wen Zhou ₃ , Qianfei Wang ₄ , Xin Gao _{1,

2} , Tao Cheng _{1,

2} , Jiaxi Zhou _{1,

2}

Affiliation

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.

中文翻译：

人类巨核细胞的细胞异质性和免疫亚群的表征

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。通过在体外进行人类巨核细胞生成的动态单细胞转录组景观，发现MK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。

更新日期：2021-08-04

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