Single-cell analysis of embryoids reveals lineage diversification roadmaps of early human development

Yi Zheng, Robin Zhexuan Yan, Shiyu Sun, Mutsumi Kobayashi, Lifeng Xiang, Ran Yang, Alexander Goedel, Yu Kang, Xufeng Xue, Sajedeh Nasr Esfahani, Yue Liu, Agnes M. Resto Irizarry, Weisheng Wu, Yunxiu Li, Weizhi Ji, Yuyu Niu, Kenneth R. Chien, Tianqing Li, Toshihiro Shioda, Jianping Fu

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Despite its clinical and fundamental importance, our understanding of early human development remains limited. Stem cell-derived, embryo-like structures (or embryoids) allowing studies of early development without using natural embryos can potentially help fill the knowledge gap of human development. Herein, transcriptome at the single-cell level of a human embryoid model was profiled at different time points. Molecular maps of lineage diversifications from the pluripotent human epiblast toward the amniotic ectoderm, primitive streak/mesoderm, and primordial germ cells were constructed and compared with in vivo primate data. The comparative transcriptome analyses reveal a critical role of NODAL signaling in human mesoderm and primordial germ cell specification, which is further functionally validated. Through comparative transcriptome analyses and validations with human blastocysts and in vitro cultured cynomolgus embryos, we further proposed stringent criteria for distinguishing between human blastocyst trophectoderm and early amniotic ectoderm cells.

Original languageEnglish (US)
Pages (from-to)1402-1419.e8
JournalCell Stem Cell
Issue number9
StatePublished - Sep 1 2022
Externally publishedYes


  • NODAL signaling
  • amnion
  • human embryoid
  • mesoderm
  • microfluidics
  • primate development
  • primitive streak
  • primordial germ cell
  • single-cell transcriptome
  • trophoblast

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology


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