Single-cell analysis of ploidy and the transcriptome reveals functional and spatial divergency in murine megakaryopoiesis
Single-cell analysis of ploidy and the transcriptome reveals functional and spatial divergency in murine megakaryopoiesis
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倍性和转录组的单细胞分析揭示了小鼠巨核细胞生成的功能和空间差异。
DOI：
10.1182/blood.2021010697
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发表时间：
2021-10-07
期刊：
影响因子：
20.3
通讯作者：
Wang, Qian-Fei
中科院分区：
文献类型：
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作者：
Sun, Shu;Jin, Chen;Wang, Qian-Fei
巨核细胞（Megakaryocytes，MKs）是血小板的前体细胞，在造血干细胞（hematopoietic stem cell，HSC）的维持和免疫中起重要作用。然而，目前还不知道这些不同的程序是由单个群体还是由不同的细胞子集执行的。在此，我们根据倍性（2N-32 N）从小鼠和人类供体的骨髓（BM）中手动分离了初级CD 41（+）MK，并进行了单细胞RNA测序分析。我们发现，细胞异质性存在于3个不同的亚群，拥有相关的血小板生成，HSC生态位相互作用，炎症反应的基因签名。小鼠骨髓的原位免疫染色表明，血小板生成和HSC小生境相关的MK分别与血管和HSC物理接近。在血液剪切力作用下可生成血小板的前血小板主要在血小板生成亚群上形成。值得注意的是，炎症反应亚群，通常由低倍性LSP 1（+）和CD 53（+）MK组成，
Megakaryocytes (MKs), the platelet progenitor cells, play important roles in hematopoietic stem cell (HSC) maintenance and immunity. However, it is not known whether these diverse programs are executed by a single population or by distinct subsets of cells. Here, we manually isolated primary CD41(+) MKs fromthe bonemarrow (BM) ofmice and human donors based on ploidy (2N-32N) and performed single-cell RNA sequencing analysis. We found that cellular heterogeneity existed within 3 distinct subpopulations that possess gene signatures related to platelet generation, HSC niche interaction, and inflammatory responses. In situ immunostaining of mouse BM demonstrated that platelet generation and the HSC niche-related MKs were in close physical proximity to blood vessels and HSCs, respectively. Proplatelets, which could give rise to platelets under blood shear forces, were predominantly formed on a platelet generation subset. Remarkably, the inflammatory responses subpopulation, consisting generally of low-ploidy LSP1(+) and CD53(+) MKs (