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