中国科学院分子细胞科学卓越创新中心（生物化学与细胞生物学研究所）景乃禾研究组、中国科学院-马普学会计算生物学伙伴研究所韩敬东研究组与中国科学院广州生物医药与健康研究院/广州再生医学与健康广东省实验室彭广敦课题组，共同合作报道了小鼠早期胚胎发育过程中全胚层谱系发生的时空转录组图谱。2019年8月22日出版的《自然》发表了这项成果。

研究人员报道了从原肠胚前期到后期发育过程中胚层中确定位置的细胞群的空间分辨转录组。这种时空转录组提供了高分辨率的数字化原位基因表达谱，揭示了组织谱系的分子图谱，并定义了时间和空间中多潜能性的连续状态。转录组进一步鉴定了驱动谱系分化和组织成型的分子决定网络，体现了Hippo-Yap信号传导在胚层发育中的作用，并揭示内脏内胚层在早期小鼠胚胎中对内胚层的贡献。

据悉，在小鼠胚胎的着床后发育期间，早期外胚层中内细胞团的后代从初始状态转变为活化的多潜能状态。同时，胚层形成并细胞谱系分化，从而建立胚胎发生的蓝图。命运映射和谱系分析研究表明，胚胎层不同区域的细胞在原肠胚形成期间获得位置特异性细胞命运。细胞命运的区域化发生在基本成体形成之前，这在脊椎动物胚胎中是保守的，并且其机制有助于理解胚胎编程和干细胞转化研究。然而，目前还没有对谱系分离和着床后胚胎的组织结构的全基因组分子注释。

Title: Molecular architecture of lineage allocation and tissue organization in early mouse embryo

Author: Guangdun Peng, Shengbao Suo, Guizhong Cui, Fang Yu, Ran Wang, Jun Chen, Shirui Chen, Zhiwen Liu, Guoyu Chen, Yun Qian, Patrick P. L. Tam, Jing-Dong J. Han, Naihe Jing

Issue&Volume: Volume 572 Issue 7770

Abstract: During post-implantation development of the mouse embryo, descendants of the inner cell mass in the early epiblast transit from the naive to primed pluripotent state1. Concurrently, germ layers are formed and cell lineages are specified, leading to the establishment of the blueprint for embryogenesis. Fate-mapping and lineage-analysis studies have revealed that cells in different regions of the germ layers acquire location-specific cell fates during gastrulation25. The regionalization of cell fates preceding the formation of the basic body planthe mechanisms of which are instrumental for understanding embryonic programming and stem-cell-based translational studyis conserved in vertebrate embryos68. However, a genome-wide molecular annotation of lineage segregation and tissue architecture of the post-implantation embryo has yet to be undertaken. Here we report a spatially resolved transcriptome of cell populations at defined positions in the germ layers during development from pre- to late-gastrulation stages. This spatiotemporal transcriptome provides high-resolution digitized in situ gene-expression profiles, reveals the molecular genealogy of tissue lineages and defines the continuum of pluripotency states in time and space. The transcriptome further identifies the networks of molecular determinants that drive lineage specification and tissue patterning, supports a role of HippoYap signalling in germ-layer development and reveals the contribution of visceral endoderm to the endoderm in the early mouse embryo.

DOI: 10.1038/s41586-019-1469-8

Source:https://www.nature.com/articles/s41586-019-1469-8