PMID- 35709828 OWN - NLM STAT- MEDLINE VI - 609 IP - 7925 TI - Spatial profiling of early primate gastrulation in utero. PG - 136-143 CI - © 2022. The Author(s), under exclusive licence to Springer Nature Limited. LA - eng PT - Journal Article PL - England TA - Nature JT - Nature JID - 0410462 IS - 1476-4687 (Electronic) LID - 10.1038/s41586-022-04953-1 [doi] FAU - Bergmann, Sophie AU - Bergmann S AD - Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. AD - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. AD - Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK. FAU - Penfold, Christopher A AU - Penfold CA AUID- ORCID: http://orcid.org/0000-0001-5823-4705 AD - Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. AD - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. AD - Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK. AD - Wellcome Trust-Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK. FAU - Slatery, Erin AU - Slatery E AUID- ORCID: http://orcid.org/0000-0002-9097-6618 AD - Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. AD - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. AD - Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK. FAU - Siriwardena, Dylan AU - Siriwardena D AD - Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. AD - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. AD - Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK. FAU - Drummer, Charis AU - Drummer C AD - Research Platform Degenerative Diseases, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany. AD - DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany. FAU - Clark, Stephen AU - Clark S AUID- ORCID: http://orcid.org/0000-0002-6183-491X AD - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. AD - Epigenetics Programme, Babraham Institute, Cambridge, UK. FAU - Strawbridge, Stanley E AU - Strawbridge SE AUID- ORCID: http://orcid.org/0000-0003-0273-0835 AD - Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. AD - Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK. FAU - Kishimoto, Keiko AU - Kishimoto K AD - Department of Marmoset Biology and Medicine, Central Institute for Experimental Animals, Kawasaki, Japan. FAU - Vickers, Alice AU - Vickers A AUID- ORCID: http://orcid.org/0000-0001-9149-4744 AD - Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, London, UK. FAU - Tewary, Mukul AU - Tewary M AD - Centre for Stem Cells and Regenerative Medicine, King's College London, Guy's Hospital, London, UK. FAU - Kohler, Timo N AU - Kohler TN AUID- ORCID: http://orcid.org/0000-0003-1949-0655 AD - Department of Biochemistry, University of Cambridge, Cambridge, UK. FAU - Hollfelder, Florian AU - Hollfelder F AUID- ORCID: http://orcid.org/0000-0002-1367-6312 AD - Department of Biochemistry, University of Cambridge, Cambridge, UK. FAU - Reik, Wolf AU - Reik W AUID- ORCID: http://orcid.org/0000-0003-0216-9881 AD - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. AD - Epigenetics Programme, Babraham Institute, Cambridge, UK. FAU - Sasaki, Erika AU - Sasaki E AUID- ORCID: http://orcid.org/0000-0002-0415-5400 AD - Department of Marmoset Biology and Medicine, Central Institute for Experimental Animals, Kawasaki, Japan. FAU - Behr, Rüdiger AU - Behr R AUID- ORCID: http://orcid.org/0000-0001-8816-6619 AD - Research Platform Degenerative Diseases, German Primate Center, Leibniz Institute for Primate Research, Göttingen, Germany. AD - DZHK (German Center for Cardiovascular Research), partner site Göttingen, Göttingen, Germany. FAU - Boroviak, Thorsten E AU - Boroviak TE AUID- ORCID: http://orcid.org/0000-0001-8703-8949 AD - Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. teb45@cam.ac.uk. AD - Centre for Trophoblast Research, University of Cambridge, Cambridge, UK. teb45@cam.ac.uk. AD - Jeffrey Cheah Biomedical Centre, Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK. teb45@cam.ac.uk. IS - 0028-0836 (Linking) SB - IM MH - Animals MH - *Callithrix/embryology MH - Cell Differentiation MH - Embryo, Mammalian/cytology/embryology MH - Endoderm/cytology/embryology MH - Female MH - *Gastrulation MH - Gene Expression Profiling MH - Germ Layers/cytology/embryology MH - Humans MH - Pluripotent Stem Cells/cytology MH - *Uterus PMC - PMC7614364 DCOM- 20220908 LR - 20240212 DP - 202209 DEP - 20220616 AB - 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 tissues1-3. Elucidating the molecular framework of axis formation in vivo is fundamental for our understanding of human development4-6 and to advance stem-cell-based regenerative approaches7. 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.