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Nat Methods. 2014 Aug;11(8):847-54. doi: 10.1038/nmeth.3016. Epub 2014 Jun 29.

A method to recapitulate early embryonic spatial patterning in human embryonic stem cells.

Author information

1
1] Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, USA. [2] Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, USA. [3].
2
1] Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, USA. [2] Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, USA.
3
Center for Studies in Physics and Biology, The Rockefeller University, New York, New York, USA.
4
Laboratory of Molecular Vertebrate Embryology, The Rockefeller University, New York, New York, USA.

Abstract

Embryos allocate cells to the three germ layers in a spatially ordered sequence. Human embryonic stem cells (hESCs) can generate the three germ layers in culture; however, differentiation is typically heterogeneous and spatially disordered. We show that geometric confinement is sufficient to trigger self-organized patterning in hESCs. In response to BMP4, colonies reproducibly differentiated to an outer trophectoderm-like ring, an inner ectodermal circle and a ring of mesendoderm expressing primitive-streak markers in between. Fates were defined relative to the boundary with a fixed length scale: small colonies corresponded to the outer layers of larger ones. Inhibitory signals limited the range of BMP4 signaling to the colony edge and induced a gradient of Activin-Nodal signaling that patterned mesendodermal fates. These results demonstrate that the intrinsic tendency of stem cells to make patterns can be harnessed by controlling colony geometries and provide a quantitative assay for studying paracrine signaling in early development.

PMID:
24973948
PMCID:
PMC4341966
DOI:
10.1038/nmeth.3016
[Indexed for MEDLINE]
Free PMC Article
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