Molecular and functional characterizations of gastrula organizer cells derived from human embryonic stem cells

Nadav Sharon, Ishay Mor, Tamar Golan-Lev, Abraham Fainsod*, Nissim Benvenisty

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

The Spemann-Mangold organizer is the structure that provides the signals, which initiate pattern formation in the developing vertebrate embryo, affecting the main body axes. Very little is known about axial induction in the gastrulating human embryo, as research is hindered by obvious ethical restrictions. Human embryonic stem cells (hESCs) are pluripotent cells derived from the pregastrula embryo that can differentiate in culture following a program similar to normal embryonic development but without pattern formation. Here, we show that in hESC-derived embryoid bodies, we can induce differentiation of cells that harbor markers and characteristics of the gastrula-organizer. Moreover, genetic labeling of these cells enabled their purification, and the discovery of a comprehensive set of their secreted proteins, cell surface receptors, and nuclear factors characteristic of the organizer. Remarkably, transplantation of cell populations enriched for the putative human organizer into frog embryos induced a secondary axis. Our research demonstrates that the human organizer can be induced in vitro and paves the way for the study of pattern formation and the initial regulation of body axis establishment in humans.

Original languageAmerican English
Pages (from-to)600-608
Number of pages9
JournalStem Cells
Volume29
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • Gastrulation
  • Human development
  • Human embryonic stem cells
  • Organizer

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