The ontogeny of the human haematopoietic system during fetal development has previously been characterized mainly through careful microscopic observations¹. Here we reconstruct a phylogenetic tree of blood development using whole-genome sequencing of 511 single-cell-derived haematopoietic colonies from healthy human fetuses at 8 and 18 weeks after conception, coupled with deep targeted sequencing of tissues of known embryonic origin. We found that, in healthy fetuses, individual haematopoietic progenitors acquire tens of somatic mutations by 18 weeks after conception. We used these mutations as barcodes and timed the divergence of embryonic and extra-embryonic tissues during development, and estimated the number of blood antecedents at different stages of embryonic development. Our data support a hypoblast origin of the extra-embryonic mesoderm and primitive blood in humans.

胎儿发育期间人类造血系统的个体发育以前主要通过仔细的显微镜观察来表征¹ 。在这里，我们利用对受孕后 8 周和 18 周健康人类胎儿的 511 个单细胞衍生造血集落进行全基因组测序，并结合对已知胚胎起源组织的深度靶向测序，重建了血液发育的系统发育树。我们发现，在健康胎儿中，个体造血祖细胞在受孕后 18 周时获得了数十种体细胞突变。我们使用这些突变作为条形码，对发育过程中胚胎和胚胎外组织的分歧进行计时，并估计胚胎发育不同阶段的血液祖先的数量。我们的数据支持人类胚胎外中胚层和原始血液的下胚层起源。