NANOG and CDX2 pattern distinct subtypes of human mesoderm during exit from pluripotency

Sasha Mendjan, Victoria L Mascetti, Daniel Ortmann, Mariaestela Ortiz, Dyah W Karjosukarso, Yifan Ng, Thomas Moreau, Roger A Pedersen

Research output: Contribution to journalArticle (Academic Journal)peer-review

124 Citations (Scopus)


Mesoderm is induced at the primitive streak (PS) and patterns subsequently into mesodermal subtypes and organ precursors. It is unclear whether mesoderm induction generates a multipotent PS progenitor or several distinct ones with restricted subtype potentials. We induced mesoderm in human pluripotent stem cells with ACTIVIN and BMP or with GSK3-β inhibition. Both approaches induced BRACHYURY(+) mesoderm of distinct PS-like identities, which had differing patterning potential. ACTIVIN and BMP-induced mesoderm patterned into cardiac but not somitic subtypes. Conversely, PS precursors induced by GSK3-β inhibition did not generate lateral plate and cardiac mesoderm and favored instead somitic differentiation. The mechanism of these cell fate decisions involved mutual repression of NANOG and CDX2. Although NANOG was required for cardiac specification but blocked somitic subtypes, CDX2 was required for somitic mesoderm but blocked cardiac differentiation. In sum, rather than forming a common PS progenitor, separate induction mechanisms distinguish human mesoderm subtypes.

Original languageEnglish
Pages (from-to)310-325
Number of pages16
JournalCell Stem Cell
Issue number3
Early online date17 Jul 2014
Publication statusPublished - 4 Sept 2014

Bibliographical note

Copyright © 2014 Elsevier Inc. All rights reserved.


  • Activins/metabolism
  • Body Patterning
  • Bone Morphogenetic Proteins/metabolism
  • CDX2 Transcription Factor
  • Cell Line
  • Cell Lineage
  • Fetal Proteins/metabolism
  • Glycogen Synthase Kinase 3/antagonists & inhibitors
  • Glycogen Synthase Kinase 3 beta
  • Homeodomain Proteins/metabolism
  • Humans
  • Mesoderm/cytology
  • Myocardium/cytology
  • Myocytes, Smooth Muscle/cytology
  • Nanog Homeobox Protein
  • Pluripotent Stem Cells/cytology
  • Primitive Streak/cytology
  • Regulatory Sequences, Nucleic Acid/genetics
  • Signal Transduction
  • T-Box Domain Proteins/metabolism


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