A method to recapitulate early embryonic spatial patterning in human embryonic stem cells
By A. Warmflash, Benoit Sorre, F. Etoc, Eric D. Siggia, Ali H. Brivanlou. Nature Methods, 2014
806 citations recorded by the source corpus.
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.
Subfields: Biomedical Engineering, Cell Biology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/f50e7efe4fe34da5d24993aa8ea20f9630909b45
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Molecular Biology
Citations in the corpus
- Making muscle: skeletal myogenesis in vivo and in vitro (2017, background): “…of cell-cell and cell-ECM interactions in controlling early stages of mesoderm differentiation: human PSCs (hPSCs) exposed to identical media will adopt distinct cell fate depending on their precise in vitro organization and volumetric cell density (Kempf et al., 2016; Warmflash et al., 2014).”