NANOG and CDX2 Pattern Distinct Subtypes of Human Mesoderm during Exit from Pluripotency

作者：Mendjan Sasha^*; Mascetti Victoria L; Ortmann Daniel; Ortiz Mariaestela; Karjosukarso Dyah W; Ng Yifan; Moreau Thomas; Pedersen Roger A

来源：Cell Stem Cell, 2014, 15(3): 310-325.

DOI：10.1016/j.stem.2014.06.006

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-beta 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-beta 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 NANOGand 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.

• 出版日期2014-9-4