Microgel culture and spatial identity mapping elucidate the signalling requirements for primate epiblast and amnion formation.

Autor:	Munger C; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK.; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge CB2 1QW, UK., Kohler TN; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK.; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge CB2 1QW, UK., Slatery E; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK., Ellermann AL; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge CB2 1QW, UK., Bergmann S; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK., Penfold CA; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK.; Wellcome Trust - Cancer Research UK Gurdon Institute, Henry Wellcome Building of Cancer and Developmental Biology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK., Ampartzidis I; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK., Chen Y; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK., Hollfelder F; Department of Biochemistry, University of Cambridge, Hopkins Building, Tennis Court Road, Cambridge CB2 1QW, UK., Boroviak TE; Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Centre for Trophoblast Research, University of Cambridge, Downing Site, Cambridge CB2 3EG, UK.; Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Jeffrey Cheah Biomedical Centre, Puddicombe Way, Cambridge CB2 0AW, UK.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2022 Oct 15; Vol. 149 (20). Date of Electronic Publication: 2022 Sep 20.
DOI:	10.1242/dev.200263
Abstrakt:	The early specification and rapid growth of extraembryonic membranes are distinctive hallmarks of primate embryogenesis. These complex tasks are resolved through an intricate combination of signals controlling the induction of extraembryonic lineages and, at the same time, safeguarding the pluripotent epiblast. Here, we delineate the signals orchestrating primate epiblast and amnion identity. We encapsulated marmoset pluripotent stem cells into agarose microgels and identified culture conditions for the development of epiblast- and amnion-spheroids. Spatial identity mapping authenticated spheroids generated in vitro by comparison with marmoset embryos in vivo. We leveraged the microgel system to functionally interrogate the signalling environment of the post-implantation primate embryo. Single-cell profiling of the resulting spheroids demonstrated that activin/nodal signalling is required for embryonic lineage identity. BMP4 promoted amnion formation and maturation, which was counteracted by FGF signalling. Our combination of microgel culture, single-cell profiling and spatial identity mapping provides a powerful approach to decipher the essential cues for embryonic and extraembryonic lineage formation in primate embryogenesis. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2022. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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