Format

Send to

Choose Destination
Cell Stem Cell. 2014 Sep 4;15(3):310-325. doi: 10.1016/j.stem.2014.06.006. Epub 2014 Jul 18.

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

Author information

1
The Anne McLaren Laboratory for Regenerative Medicine, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0SZ, UK. Electronic address: sm687@cam.ac.uk.
2
The Anne McLaren Laboratory for Regenerative Medicine, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0SZ, UK.
3
The Anne McLaren Laboratory for Regenerative Medicine, Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0SZ, UK; Department of Surgery, University of Cambridge, Cambridge CB2 0SZ, UK. Electronic address: ralp2@cam.ac.uk.

Abstract

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.

PMID:
25042702
DOI:
10.1016/j.stem.2014.06.006
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center