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Negretti, Nicholas M; Plosa, Erin J; Benjamin, John T; Schuler, Bryce A; Habermann, A Christian; Jetter, Christopher S; Gulleman, Peter; Bunn, Claire; Hackett, Alice N; Ransom, Meaghan; Taylor, Chase J; Nichols, David; Matlock, Brittany K; Guttentag, Susan H; Blackwell, Timothy S; Banovich, Nicholas E; Kropski, Jonathan A; Sucre, Jennifer M S
Development (Cambridge), 12/2021, Letnik: 148, Številka: 24Journal Article
Lung organogenesis requires precise timing and coordination to effect spatial organization and function of the parenchymal cells. To provide a systematic broad-based view of the mechanisms governing the dynamic alterations in parenchymal cells over crucial periods of development, we performed a single-cell RNA-sequencing time-series yielding 102,571 epithelial, endothelial and mesenchymal cells across nine time points from embryonic day 12 to postnatal day 14 in mice. Combining computational fate-likelihood prediction with RNA in situ hybridization and immunofluorescence, we explore lineage relationships during the saccular to alveolar stage transition. The utility of this publicly searchable atlas resource (www.sucrelab.org/lungcells) is exemplified by discoveries of the complexity of type 1 pneumocyte function and characterization of mesenchymal Wnt expression patterns during the saccular and alveolar stages - wherein major expansion of the gas-exchange surface occurs. We provide an integrated view of cellular dynamics in epithelial, endothelial and mesenchymal cell populations during lung organogenesis.
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in: SICRIS
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