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Tracking early mammalian organogenesis - prediction and validation of differentiation trajectories at whole organism scale.
Imaz-Rosshandler, Ivan; Rode, Christina; Guibentif, Carolina; Harland, Luke T G; Ton, Mai-Linh N; Dhapola, Parashar; Keitley, Daniel; Argelaguet, Ricard; Calero-Nieto, Fernando J; Nichols, Jennifer; Marioni, John C; de Bruijn, Marella F T R; Göttgens, Berthold.
Afiliación
  • Imaz-Rosshandler I; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK.
  • Rode C; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
  • Guibentif C; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
  • Harland LTG; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
  • Ton MN; Department of Microbiology and Immunology, University of Gothenburg, 405 30 Gothenburg, Sweden.
  • Dhapola P; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK.
  • Keitley D; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
  • Argelaguet R; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK.
  • Calero-Nieto FJ; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
  • Nichols J; Division of Molecular Hematology, Lund Stem Cell Center, Lund University, 221 00 Lund, Sweden.
  • Marioni JC; Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK.
  • de Bruijn MFTR; Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.
  • Göttgens B; Altos Labs Cambridge Institute, Granta Park, Cambridge CB21 6GP, UK.
Development ; 151(3)2024 Feb 01.
Article en En | MEDLINE | ID: mdl-37982461
Early organogenesis represents a key step in animal development, during which pluripotent cells diversify to initiate organ formation. Here, we sampled 300,000 single-cell transcriptomes from mouse embryos between E8.5 and E9.5 in 6-h intervals and combined this new dataset with our previous atlas (E6.5-E8.5) to produce a densely sampled timecourse of >400,000 cells from early gastrulation to organogenesis. Computational lineage reconstruction identified complex waves of blood and endothelial development, including a new programme for somite-derived endothelium. We also dissected the E7.5 primitive streak into four adjacent regions, performed scRNA-seq and predicted cell fates computationally. Finally, we defined developmental state/fate relationships by combining orthotopic grafting, microscopic analysis and scRNA-seq to transcriptionally determine cell fates of grafted primitive streak regions after 24 h of in vitro embryo culture. Experimentally determined fate outcomes were in good agreement with computationally predicted fates, demonstrating how classical grafting experiments can be revisited to establish high-resolution cell state/fate relationships. Such interdisciplinary approaches will benefit future studies in developmental biology and guide the in vitro production of cells for organ regeneration and repair.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organogénesis / Gastrulación Límite: Animals Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organogénesis / Gastrulación Límite: Animals Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido