Molecular recording of mammalian embryogenesis
Molecular recording of mammalian embryogenesis
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DOI：
10.1038/s41586-019-1184-5
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发表时间：
2019-06-06
期刊：
影响因子：
64.8
通讯作者：
Weissman, Jonathan S.
中科院分区：
文献类型：
--
作者：
Chan, Michelle M.;Smith, Zachary D.;Weissman, Jonathan S.
个体发生描述了从单个全能细胞到复杂的多细胞生物体的出现。这一领域在哺乳动物中特别具有挑战性，因为这些动物的自我更新和分化之间的关系不确定，祖先领域大小的变化以及内部妊娠。在这里，我们提出了一个灵活的，高信息，多通道的分子记录仪与单细胞读数，并将其作为一个不断发展的谱系示踪剂组装小鼠细胞命运图从受精到原肠胚形成。通过将谱系信息与单细胞RNA测序谱相结合，我们概括了不同组织类型之间的典型发育关系，并揭示了胚胎外和胚胎起源的内胚层细胞几乎完全的转录收敛。最后，我们应用我们的细胞命运图来估计胚胎祖细胞的数量和它们在规范过程中的不对称分配程度。我们的方法能够大规模并行、高分辨率地记录哺乳动物系统中的谱系和其他信息，这将促进理解发育过程的定量框架的构建。
Ontogeny describes the emergence of complex multicellular organisms from single totipotent cells. This field is particularly challenging in mammals, owing to the indeterminate relationship between self-renewal and differentiation, variation in progenitor field sizes, and internal gestation in these animals. Here we present a flexible, high-information, multi-channel molecular recorder with a single-cell readout and apply it as an evolving lineage tracer to assemble mouse cell-fate maps from fertilization through gastrulation. By combining lineage information with single-cell RNA sequencing profiles, we recapitulate canonical developmental relationships between different tissue types and reveal the nearly complete transcriptional convergence of endodermal cells of extra-embryonic and embryonic origins. Finally, we apply our cell-fate maps to estimate the number of embryonic progenitor cells and their degree of asymmetric partitioning during specification. Our approach enables massively parallel, high-resolution recording of lineage and other information in mammalian systems, which will facilitate the construction of a quantitative framework for understanding developmental processes.