Combinatorial signals of activin/nodal and bone morphogenic protein regulate the early lineage segregation of human embryonic stem cells

Zhao Wu, Wei Zhang, Guibin Chen, Lu Cheng, Jing Liao, Nannan Jia, Yuan Gao, Huiming Dai, Jinduo Yuan, Linzhao Cheng, Lei Xiao

Research output: Contribution to journalArticle


Cell fate commitment of pre-implantation blastocysts, to either the inner cell mass or trophoblast, is the first step in cell lineage segregation of the developing human embryo. However, the intercellular signals that control fate determination of these cells remain obscure. Human embryonic stem cells (hESCs) provide a unique model for studying human early embryonic development. We have previously shown that Activin/Nodal signaling contributes to maintaining pluripotency of hESCs, which are derivatives of the inner cell mass. Here we further demonstrate that the inhibition of Activin/Nodal signaling results in the loss of hESC pluripotency and trophoblast differentiation, similar to BMP4-induced trophoblast differentiation from hESCs. We also show that the trophoblast induction effect of BMP4 correlates with and depends on the inhibition of Activin/Nodal signaling. However, the activation of BMP signaling is still required for trophoblast differentiation when Activin/Nodal signaling is inhibited. These data reveal that the early lineage segregation of hESCs is determined by the combinatorial signals of Activin/Nodal and BMP.

Original languageEnglish (US)
Pages (from-to)24991-25002
Number of pages12
JournalJournal of Biological Chemistry
Issue number36
Publication statusPublished - Sep 5 2008


ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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