Spatial profiling of early primate gastrulation in utero.

Autor: Bergmann S; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.; Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK., Penfold CA; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.; Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.; Wellcome Trust-Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK., Slatery E; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.; Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK., Siriwardena D; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.; Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK., Drummer C; Research Platform Degenerative Diseases, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany., Clark S; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.; Epigenetics Programme, Babraham Institute, Cambridge, UK., Strawbridge SE; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK.; Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK., Kishimoto K; Department of Marmoset Biology and Medicine, Central Institute for Experimental Animals, Kawasaki, Japan., Vickers A; Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, London, UK., Tewary M; Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, London, UK., Kohler TN; Department of Biochemistry, University of Cambridge, Cambridge, UK., Hollfelder F; Department of Biochemistry, University of Cambridge, Cambridge, UK., Reik W; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.; Epigenetics Programme, Babraham Institute, Cambridge, UK., Sasaki E; Department of Marmoset Biology and Medicine, Central Institute for Experimental Animals, Kawasaki, Japan., Behr R; Research Platform Degenerative Diseases, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany.; DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany., Boroviak TE; Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. teb45@cam.ac.uk.; Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. teb45@cam.ac.uk.; Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK. teb45@cam.ac.uk.
Jazyk: angličtina
Zdroj: Nature [Nature] 2022 Sep; Vol. 609 (7925), pp. 136-143. Date of Electronic Publication: 2022 Jun 16.
DOI: 10.1038/s41586-022-04953-1
Abstrakt: Gastrulation controls the emergence of cellular diversity and axis patterning in the early embryo. In mammals, this transformation is orchestrated by dynamic signalling centres at the interface of embryonic and extraembryonic tissues 1-3 . Elucidating the molecular framework of axis formation in vivo is fundamental for our understanding of human development 4-6 and to advance stem-cell-based regenerative approaches 7 . Here we illuminate early gastrulation of marmoset embryos in utero using spatial transcriptomics and stem-cell-based embryo models. Gaussian process regression-based 3D transcriptomes delineate the emergence of the anterior visceral endoderm, which is hallmarked by conserved (HHEX, LEFTY2, LHX1) and primate-specific (POSTN, SDC4, FZD5) factors. WNT signalling spatially coordinates the formation of the primitive streak in the embryonic disc and is counteracted by SFRP1 and SFRP2 to sustain pluripotency in the anterior domain. Amnion specification occurs at the boundaries of the embryonic disc through ID1, ID2 and ID3 in response to BMP signalling, providing a developmental rationale for amnion differentiation of primate pluripotent stem cells (PSCs). Spatial identity mapping demonstrates that primed marmoset PSCs exhibit the highest similarity to the anterior embryonic disc, whereas naive PSCs resemble the preimplantation epiblast. Our 3D transcriptome models reveal the molecular code of lineage specification in the primate embryo and provide an in vivo reference to decipher human development.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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