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The processes of primitive streak formation and fate specification in the mammalian epiblast rely on complex interactions between morphogens and tissue organization. Little is known about how these instructive cues functionally interact to regulate gastrulation. We interrogated the interplay between tissue organization and morphogens by using human induced pluripotent stem cells (hiPSCs) down-regulated for the morphogen regulator GLYPICAN-4, in which defects in tight junctions result in areas of disrupted epithelial integrity. Remarkably, this phenotype does not affect hiPSC stemness, but impacts on cell fate acquisition processes. Strikingly, cells within disrupted areas become competent to perceive BMP4 and ACTIVIN A/NODAL gastrulation signals and thus, differentiate into mesendoderm. Yet, disruption of epithelial integrity prolongs temporal activation of BMP4 and ACTIVIN A/NODAL downstream effectors and correlates with enhanced hiPSC endoderm/mesoderm differentiation potential. Altogether, our results disclose epithelial cell integrity as a key determinant of TGF-β activity and highlight a new mechanism guiding morphogen sensing and spatial cell fate change within an epithelium.

The Ocean Gene Atlas is a web service to explore the biogeography of genes from marine planktonic organisms. It allows users to query protein or nucleotide sequences against global ocean reference gene catalogs. With just one click, the abundance and location of target sequences are visualized on world maps as well as their taxonomic distribution. Interactive results panels allow for adjusting cutoffs for homology and displaying the abundances of genes in the context of environmental features (temperature, nutrients, etc.) measured at the time of sampling. The ease of use enables non-bioinformaticians to explore quantitative and contextualized information on genes of interest in the global ocean ecosystem. Currently the Ocean Gene Atlas is deployed with i) the Ocean Microbial Reference Gene Catalog (OM-RGC) comprising 40 million non-redundant mostly prokaryotic gene sequences, and ii) the Marine Atlas of Tara Ocean Unigenes (MATOU) composed of >116 million eukaryote unigenes, both produced by the Tara Oceans sequencing effort. Additional datasets will be added upon availability of further marine environmental datasets that provide the required complement of sequence assemblies, raw reads and contextual environmental parameters. Ocean Gene Atlas is a freely-available web service at: http://tara-oceans.mio.osupytheas.fr/ocean-gene-atlas/.