造血干细胞异质性和与年龄相关的血小板偏倚在进化上是保守的。

Hematopoietic stem cell heterogeneity and age-associated platelet bias are evolutionarily conserved.

机构信息

MRC Molecular Hematology Unit, MRC Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.

Oxford NIHR BRC Haematology Theme, University of Oxford, Oxford, UK.

出版信息

Sci Immunol. 2024 Aug 23;9(98):eadk3469. doi: 10.1126/sciimmunol.adk3469.

DOI:10.1126/sciimmunol.adk3469

PMID:39178276

Abstract

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.

摘要

造血干细胞（HSCs）在临床骨髓（BM）移植后可重建多谱系人类造血，并为某些血液系统恶性肿瘤的起源细胞。尽管 HSCs 提供多谱系植入，但单个鼠 HSCs 具有谱系偏向性，并且对血细胞谱系的贡献不均等。在这里，我们在与分子条码化成人 BM HSCs 异种移植后对小鼠进行了高通量单细胞 RNA 测序。我们证明，人类个体 BM HSCs 在功能和转录上也具有谱系偏向性。具体来说，我们鉴定出血小板偏向性和多谱系人类 HSCs。来自年轻和老年 BM 的单个 HSCs 的转录组的定量比较表明，血小板偏向性 HSCs 的比例及其转录血小板启动的水平都随着年龄的增长而增加。因此，血小板偏向性 HSCs 及其在衰老过程中增加的患病率和转录血小板启动是哺乳动物进化的保守特征。