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Lineage tracing of human embryonic development and foetal haematopoiesis through somatic mutations
bioRxiv - Genomics Pub Date : 2020-05-30 , DOI: 10.1101/2020.05.29.088765
Michael Spencer Chapman , Anna Maria Ranzoni , Brynelle Myers , Nick Williams , Tim Coorens , Emily Mitchell , Timothy Butler , Kevin J Dawson , Yvette Hooks , Luiza Moore , Jyoti Nangalia , Philip S Robinson , Elizabeth Hook , Peter J Campbell , Ana Cvejic

To date, ontogeny of the human haematopoietic system during foetal development has been characterized mainly through careful microscopic observations. Here we used whole-genome sequencing (WGS) of 511 single-cell derived haematopoietic colonies from healthy human foetuses of 8 and 18 post-conception weeks (pcw) coupled with deep targeted sequencing of tissues of known embryonic origin to reconstruct a phylogenetic tree of blood development. We found that in healthy foetuses, individual haematopoietic progenitors acquire tens of somatic mutations by 18 pcw. Using these mutations as barcodes, we 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 analysis has shown that ectoderm originates from a smaller set of blood antecedents compared to endoderm and mesoderm. Finally, our data support a hypoblast origin of the extra-embryonic mesoderm and primitive blood in humans.

中文翻译:

通过体细胞突变的人类胚胎发育和胎儿造血功能的谱系追踪

迄今为止,主要通过仔细的显微镜观察来表征胎儿发育过程中人类造血系统的个体发育。在这里,我们使用了来自受孕后8周和18周(pcw)的健康人类胎儿的511个单细胞来源的造血集落的全基因组测序(WGS),结合已知胚胎起源的组织的深度靶向测序,重建了血液发育。我们发现,在健康的胎儿中,单个造血祖细胞通过18 pcw获得数十个体细胞突变。使用这些突变作为条形码,我们在发育过程中定时了胚胎和胚外组织的分化时间,并估计了胚胎发育不同阶段的血液前体数量。我们的分析表明,与内胚层和中胚层相比,外胚层起源于较小的血液前因集合。最后,我们的数据支持人胚外中胚层和原始血液的成胚起源。
更新日期:2020-05-30
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