A Method to Recapitulate Early Embryonic Spatial Patterning in Human Embryonic Stem Cells

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2014 Jun 30

PMID 24973948

Citations 391

Authors

Aryeh Warmflash

Benoit Sorre

Fred Etoc

Eric D Siggia

Ali H Brivanlou

Affiliations

Soon will be listed here.

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.

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