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

Cornell Affiliated Author(s)

Author

A. Warmflash
B. Sorre
F. Etoc
E.D. Siggia
A.H. Brivanlou

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 confnement is suffcient 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 defned relative to the boundary with a fxed 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. © 2014 Nature America, Inc. All rights reserved.

Date Published

Journal

Nature Methods

Volume

11

Issue

8

Number of Pages

847-854,

URL

https://www.scopus.com/inward/record.uri?eid=2-s2.0-84905258655&doi=10.1038%2fnMeth.3016&partnerID=40&md5=b611f8f1f35b50b267e1ce28e7698d2b

DOI

10.1038/nMeth.3016

Research Area

Funding Source

R01GM101653
R01HD032105
PHY-0954398

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