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

Imaz-Rosshandler, Ivan (author)
Rode, Christina (author)
Guibentif, Carolina (author)
Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi,Institute of Biomedicine, Department of Microbiology and Immunology
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Harland, Luke T. G. (author)
Ton, Mai-Linh N. (author)
Dhapola, Parashar (author)
Keitley, Daniel (author)
Argelaguet, Ricard (author)
Calero-Nieto, Fernando J. (author)
Nichols, Jennifer (author)
Marioni, John C. (author)
de Bruijn, Marella F. T. R. (author)
Gottgens, Berthold (author)
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 (creator_code:org_t)
2024
2024
English.
In: DEVELOPMENT. - 0950-1991 .- 1477-9129. ; 151:3
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  • Journal article (peer-reviewed)
Abstract Subject headings
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  • 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.

Subject headings

NATURVETENSKAP  -- Biologi -- Utvecklingsbiologi (hsv//swe)
NATURAL SCIENCES  -- Biological Sciences -- Developmental Biology (hsv//eng)

Keyword

Cell fate and differentiation
Haematopoiesis
Mouse development
Single-cell transcriptomics

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