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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 LU ; Keitley, Daniel ; Argelaguet, Ricard ; Calero-Nieto, Fernando J. and Nichols, Jennifer , et al. (2024) In Development (Cambridge) 151(3). p.1-17
Abstract

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/... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cell fate and differentiation, Haematopoiesis, Mouse development, Single-cell transcriptomics
in
Development (Cambridge)
volume
151
issue
3
pages
17 pages
publisher
The Company of Biologists Ltd
external identifiers
  • scopus:85182328172
  • pmid:37982461
ISSN
0950-1991
DOI
10.1242/dev.201867
language
English
LU publication?
yes
id
638a9478-bc3b-45de-a065-62e1c940eda1
date added to LUP
2025-01-15 12:06:12
date last changed
2025-07-17 03:08:11
@article{638a9478-bc3b-45de-a065-62e1c940eda1,
  abstract     = {{<p>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 &gt;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.</p>}},
  author       = {{Imaz-Rosshandler, Ivan and Rode, Christina and Guibentif, Carolina and Harland, Luke T.G. and Ton, Mai Linh N. and Dhapola, Parashar and Keitley, Daniel and Argelaguet, Ricard and Calero-Nieto, Fernando J. and Nichols, Jennifer and Marioni, John C. and de Bruijn, Marella F.T.R. and Göttgens, Berthold}},
  issn         = {{0950-1991}},
  keywords     = {{Cell fate and differentiation; Haematopoiesis; Mouse development; Single-cell transcriptomics}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{1--17}},
  publisher    = {{The Company of Biologists Ltd}},
  series       = {{Development (Cambridge)}},
  title        = {{Tracking early mammalian organogenesis - prediction and validation of differentiation trajectories at whole organism scale}},
  url          = {{http://dx.doi.org/10.1242/dev.201867}},
  doi          = {{10.1242/dev.201867}},
  volume       = {{151}},
  year         = {{2024}},
}