期刊
NATURE METHODS
卷 11, 期 8, 页码 847-854出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH.3016
关键词
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资金
- Rockefeller University
- NYSTEM
- US National Institutes of Health [R01 HD32105, R01 GM 101653]
- US National Science Foundation [PHY-0954398]
- Human Frontier Science Program [LT000851/2011-L]
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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