Hematopoietic stem cells (HSCs) reconstitute multilineage human hematopoiesis after clinical bone marrow (BM) transplantation and are the cells of origin of some hematological malignancies. Although HSCs provide multilineage engraftment, individual murine HSCs are lineage biased and contribute unequally to blood cell lineages. Here, we performed high-throughput single-cell RNA sequencing in mice after xenograft with molecularly barcoded adult human BM HSCs. We demonstrated that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identified platelet-biased and multilineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young and aged BM showed that both the proportion of platelet-biased HSCs and their level of transcriptional platelet priming increase with age. Therefore, platelet-biased HSCs and their increased prevalence and transcriptional platelet priming during aging are conserved features of mammalian evolution.

中文翻译：

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造血干细胞异质性和与年龄相关的血小板偏差在进化上是保守的


造血干细胞（HSC）在临床骨髓（BM）移植后重建多谱系人类造血功能，并且是一些血液恶性肿瘤的起源细胞。尽管 HSC 提供多谱系移植，但个体小鼠 HSC 存在谱系偏向，并且对血细胞谱系的贡献不均等。在这里，我们对带有分子条形码的成人骨髓 HSC 异种移植后的小鼠进行了高通量单细胞 RNA 测序。我们证明人类个体 BM HSC 在功能和转录谱系上也存在偏差。具体来说，我们鉴定了血小板偏向性和多谱系人类 HSC。对来自年轻和老年 BM 的单个 HSC 的转录组进行定量比较表明，血小板偏向性 HSC 的比例及其转录血小板启动水平都随着年龄的增长而增加。因此，血小板偏向的 HSC 及其增加的患病率和衰老过程中转录血小板启动是哺乳动物进化的保守特征。