Identification and Age-dependent Increase of Platelet Biased Human Hematopoietic Stem Cells
Identification and Age-dependent Increase of Platelet Biased Human Hematopoietic Stem Cells
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DOI：
10.1101/2022.01.14.475546
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发表时间：
2022-01
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通讯作者：
Merve Aksöz;Grigore-Aristide Gafencu;B. Stoilova;M. Buono;Yiran Meng;N. A. Jakobsen;M. Metzner;Sally-Ann Clark;R. Beveridge;S. Thongjuea;P. Vyas;C. Nerlov
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作者：
Merve Aksöz;Grigore-Aristide Gafencu;B. Stoilova;M. Buono;Yiran Meng;N. A. Jakobsen;M. Metzner;Sally-Ann Clark;R. Beveridge;S. Thongjuea;P. Vyas;C. Nerlov
造血干细胞（HSC）在临床骨髓移植后重建人类多谱系造血功能，是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 具有谱系偏向性，并且对血细胞谱系的贡献不均等。现在，通过结合分子条形码成人骨髓 (BM) HSC 的异种移植和高通量单细胞 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，血小板偏向的 HSC 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，血小板偏向的 HSC 及其在衰老过程中增加的患病率和转录血小板启动作用在人类和小鼠造血过程中是保守的。一句话总结体内条形码和单细胞 RNA 测序可识别血小板偏向的人骨髓 HSC。
Hematopoietic stem cells (HSC) reconstitute multi-lineage human hematopoiesis after clinical bone marrow transplantation and are the cells-of-origin of hematological malignancies. Though HSC provide multi-lineage engraftment, individual murine HSCs are lineage-biased and contribute unequally to blood cell lineages. Now, by combining xenografting of molecularly barcoded adult human bone marrow (BM) HSCs and high-throughput single cell RNA sequencing we demonstrate that human individual BM HSCs are also functionally and transcriptionally lineage biased. Specifically, we identify platelet-biased and multi-lineage human HSCs. Quantitative comparison of transcriptomes from single HSCs from young, and aged, BM show that both the proportion of platelet-biased HSCs, and their level of transcriptional platelet priming, increases with age. Therefore, platelet-biased HSCs, as well as their increased prevalence and elevated transcriptional platelet priming during ageing, are conserved between human and murine hematopoiesis. One-Sentence Summary In vivo barcoding and single cell RNA sequencing identifies platelet-biased human bone marrow HSCs.