Tracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scale
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 (...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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The Company of Biologists
2024
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| _version_ | 1797113224010661888 |
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| author | Imaz-Rosshandler, I Rode, C Guibentif, C Harland, LTG Ton, M-LN Dhapola, P Keitley, D Argelaguet, R Calero-Nieto, FJ Nichols, J Marioni, JC de Bruijn, MFTR Göttgens, B |
| author_facet | Imaz-Rosshandler, I Rode, C Guibentif, C Harland, LTG Ton, M-LN Dhapola, P Keitley, D Argelaguet, R Calero-Nieto, FJ Nichols, J Marioni, JC de Bruijn, MFTR Göttgens, B |
| author_sort | Imaz-Rosshandler, I |
| collection | OXFORD |
| description | 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 <i>in vitro</i> 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 <i>in vitro</i> production of cells for organ regeneration and repair. |
| first_indexed | 2024-03-07T08:18:31Z |
| format | Journal article |
| id | oxford-uuid:4db63269-d099-4384-86fe-98e13b6ae4a8 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-04-23T08:25:25Z |
| publishDate | 2024 |
| publisher | The Company of Biologists |
| record_format | dspace |
| spelling | oxford-uuid:4db63269-d099-4384-86fe-98e13b6ae4a82024-04-18T10:49:21ZTracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scaleJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4db63269-d099-4384-86fe-98e13b6ae4a8EnglishSymplectic ElementsThe Company of Biologists2024Imaz-Rosshandler, IRode, CGuibentif, CHarland, LTGTon, M-LNDhapola, PKeitley, DArgelaguet, RCalero-Nieto, FJNichols, JMarioni, JCde Bruijn, MFTRGöttgens, BEarly 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 <i>in vitro</i> 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 <i>in vitro</i> production of cells for organ regeneration and repair. |
| spellingShingle | Imaz-Rosshandler, I Rode, C Guibentif, C Harland, LTG Ton, M-LN Dhapola, P Keitley, D Argelaguet, R Calero-Nieto, FJ Nichols, J Marioni, JC de Bruijn, MFTR Göttgens, B Tracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scale |
| title | Tracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scale |
| title_full | Tracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scale |
| title_fullStr | Tracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scale |
| title_full_unstemmed | Tracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scale |
| title_short | Tracking early mammalian organogenesis – prediction and validation of differentiation trajectories at whole organism scale |
| title_sort | tracking early mammalian organogenesis prediction and validation of differentiation trajectories at whole organism scale |
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