Haematopoietic stem cells drive blood production, but their population size and lifetime dynamics have not been quantified directly in humans. Here we identified 129,582 spontaneous, genome-wide somatic mutations in 140 single-cell-derived haematopoietic stem and progenitor colonies from a healthy 59-year-old man and applied population-genetics approaches to reconstruct clonal dynamics. Cell divisions from early embryogenesis were evident in the phylogenetic tree; all blood cells were derived from a common ancestor that preceded gastrulation. The size of the stem cell population grew steadily in early life, reaching a stable plateau by adolescence. We estimate the numbers of haematopoietic stem cells that are actively making white blood cells at any one time to be in the range of 50,000–200,000. We observed adult haematopoietic stem cell clones that generate multilineage outputs, including granulocytes and B lymphocytes. Harnessing naturally occurring mutations to report the clonal architecture of an organ enables the high-resolution reconstruction of somatic cell dynamics in humans.Analysis of blood from a healthy human show that haematopoietic stem cells increase rapidly in numbers through early life, reaching a stable plateau in adulthood, and contribute to myeloid and B lymphocyte populations throughout life.

中文翻译：

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从体细胞突变推断正常人血液的群体动态

造血干细胞驱动血液产生，但它们的群体规模和寿命动态尚未在人类中直接量化。在这里，我们在一名 59 岁健康男性的 140 个单细胞来源的造血干细胞和祖细胞集落中鉴定出了 129,582 个自发的全基因组体细胞突变，并应用群体遗传学方法重建克隆动态。在系统发育树中，早期胚胎发生的细胞分裂是明显的。所有血细胞都源自原肠胚形成之前的共同祖先。干细胞群的规模在生命早期稳定增长，到青春期达到稳定的平台。我们估计在任何一个时间活跃地产生白细胞的造血干细胞的数量在 50,000-200,000 之间。我们观察到产生多谱系输出的成体造血干细胞克隆，包括粒细胞和 B 淋巴细胞。利用自然发生的突变来报告器官的克隆结构，能够高分辨率重建人类体细胞动力学。对健康人血液的分析表明，造血干细胞的数量在生命早期迅速增加，在生命早期达到稳定的平台期。成年期，并在一生中对骨髓细胞和 B 淋巴细胞群体做出贡献。