Lineage tracing of human development through somatic mutations
Lineage tracing of human development through somatic mutations
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DOI：
10.1038/s41586-021-03548-6
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发表时间：
2021-05-12
期刊：
影响因子：
64.8
通讯作者：
Cvejic, Ana
中科院分区：
文献类型：
--
作者：
Spencer Chapman, Michael;Ranzoni, Anna Maria;Cvejic, Ana
在胎儿发育期间，人类造血系统的个体发生以前主要通过仔细的显微镜观察来表征（1）。在这里，我们使用全基因组测序的511个单细胞来源的造血集落，从健康的人类胎儿在受孕后8周和18周，再加上深度有针对性的测序已知的胚胎来源的组织，重建血液发育的系统发育树。我们发现，在健康的胎儿中，个体造血祖细胞在受孕后18周获得数十个体细胞突变。我们使用这些突变作为条形码，并对发育过程中胚胎和胚外组织的分化进行计时，并估计胚胎发育不同阶段的血液前身数量。我们的数据支持胚外中胚层和原始血液在人类的下胚层起源。
The ontogeny of the human haematopoietic system during fetal development has previously been characterized mainly through careful microscopic observations(1). 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.