Tracking early mammalian organogenesis - prediction and validation of differentiation trajectories at whole organism scale.

Autor:	Imaz-Rosshandler I; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK.; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.; MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, UK., Rode C; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK., Guibentif C; Department of Microbiology and Immunology, University of Gothenburg, 405 30 Gothenburg, Sweden., Harland LTG; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK.; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK., Ton MN; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK.; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK., Dhapola P; Division of Molecular Hematology, Lund Stem Cell Center, Lund University, 221 00 Lund, Sweden., Keitley D; Department of Zoology, University of Cambridge, Cambridge CB2 3EJ, UK., Argelaguet R; Epigenetics Programme, Babraham Institute, Cambridge CB22 3AT, UK.; Altos Labs Cambridge Institute, Granta Park, Cambridge CB21 6GP, UK., Calero-Nieto FJ; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK., Nichols J; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK., Marioni JC; Wellcome Sanger Institute, Wellcome Genome Campus, Saffron Walden CB10 1SA, UK.; European Molecular Biology Laboratory, European Bioinformatics Institute, Saffron Walden CB10 1SA, UK.; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK., de Bruijn MFTR; MRC Molecular Haematology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK., Göttgens B; Department of Haematology, University of Cambridge, Cambridge CB2 0RE, UK.; Wellcome-Medical Research Council Cambridge Stem Cell Institute, University of Cambridge, Cambridge CB2 0AW, UK.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2024 Feb 01; Vol. 151 (3). Date of Electronic Publication: 2024 Jan 31.
DOI:	10.1242/dev.201867
Abstrakt:	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. Competing Interests: Competing interests J.C.M. has been an employee of Genentech since September 2022. (© 2024. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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