Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity [Visium]
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ABSTRACT:
PROVIDER: PRJNA1102342 | ENA |
REPOSITORIES: ENA
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Project description:While animal models have provided key insights into conserved mechanisms of how the lung forms during development, human-specific developmental mechanisms are not always captured. To fully appreciate how developmental defects and disease states alter the function of the lungs, studies in human lung models are important. Here, we sequenced >150,000 single single-cells from 19 healthy human fetal lung tissues from gestational weeks 10-19 and identified at least 58 unique cell types/states contributing to the developing lung. We captured novel dynamic developmental trajectories from various progenitor cells that give rise to ciliated, pulmonary neuroendocrine cells, and other specialized cell types. We also identified four CFTR-expressing progenitor cell types and pinpointed the temporal emergence and spatial localization of these cell types. These developmental dynamics reveal broader epithelial cell plasticity and novel lineage hierarchies that were not previously reported. Combined with spatial transcriptomics, we identified both cell autonomous and non-cell autonomous signalling pathways that may dictate the temporal and spatial emergence of cell lineages. Finally, we showed that human pluripotent stem cell (hPSC)-derived fetal lung models capture similar cell lineage trajectories specifically through progenitor cells that express abundant levels of the CFTR gene. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from hPSC differentiations to similar developmental window.
2024-06-04 | GSE264398 | GEO
Project description:Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity [scRNAseq-fetal tissue]
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Project description:While animal models have provided key insights into conserved mechanisms of how the lung forms during development, human-specific developmental mechanisms are not always captured. To fully appreciate how developmental defects and disease states alter the function of the lungs, studies in human lung models are important. Here, we sequenced >150,000 single single-cells from 19 healthy human fetal lung tissues from gestational weeks 10-19 and identified at least 58 unique cell types/states contributing to the developing lung. We captured novel dynamic developmental trajectories from various progenitor cells that give rise to ciliated, pulmonary neuroendocrine cells, and other specialized cell types. We also identified four CFTR-expressing progenitor cell types and pinpointed the temporal emergence and spatial localization of these cell types. These developmental dynamics reveal broader epithelial cell plasticity and novel lineage hierarchies that were not previously reported. Combined with spatial transcriptomics, we identified both cell autonomous and non-cell autonomous signalling pathways that may dictate the temporal and spatial emergence of cell lineages. Finally, we showed that human pluripotent stem cell (hPSC)-derived fetal lung models capture similar cell lineage trajectories specifically through progenitor cells that express abundant levels of the CFTR gene. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from hPSC differentiations to similar developmental window.
2024-06-04 | GSE264407 | GEO
Project description:While animal models have provided key insights into conserved mechanisms of how the lung forms during development, human-specific developmental mechanisms are not always captured. To fully appreciate how developmental defects and disease states alter the function of the lungs, studies in human lung models are important. Here, we sequenced >150,000 single single-cells from 19 healthy human fetal lung tissues from gestational weeks 10-19 and identified at least 58 unique cell types/states contributing to the developing lung. We captured novel dynamic developmental trajectories from various progenitor cells that give rise to ciliated, pulmonary neuroendocrine cells, and other specialized cell types. We also identified four CFTR-expressing progenitor cell types and pinpointed the temporal emergence and spatial localization of these cell types. These developmental dynamics reveal broader epithelial cell plasticity and novel lineage hierarchies that were not previously reported. Combined with spatial transcriptomics, we identified both cell autonomous and non-cell autonomous signalling pathways that may dictate the temporal and spatial emergence of cell lineages. Finally, we showed that human pluripotent stem cell (hPSC)-derived fetal lung models capture similar cell lineage trajectories specifically through progenitor cells that express abundant levels of the CFTR gene. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from hPSC differentiations to similar developmental window.
2024-06-04 | GSE264425 | GEO
Project description:Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity [Xenium]
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Project description:While animal models have provided key insights into conserved mechanisms of how the lung forms during development, human-specific developmental mechanisms are not always captured. To fully appreciate how developmental defects and disease states alter the function of the lungs, studies in human lung models are important. Here, we sequenced >150,000 single single-cells from 19 healthy human fetal lung tissues from gestational weeks 10-19 and identified at least 58 unique cell types/states contributing to the developing lung. We captured novel dynamic developmental trajectories from various progenitor cells that give rise to ciliated, pulmonary neuroendocrine cells, and other specialized cell types. We also identified four CFTR-expressing progenitor cell types and pinpointed the temporal emergence and spatial localization of these cell types. These developmental dynamics reveal broader epithelial cell plasticity and novel lineage hierarchies that were not previously reported. Combined with spatial transcriptomics, we identified both cell autonomous and non-cell autonomous signalling pathways that may dictate the temporal and spatial emergence of cell lineages. Finally, we showed that human pluripotent stem cell (hPSC)-derived fetal lung models capture similar cell lineage trajectories specifically through progenitor cells that express abundant levels of the CFTR gene. Overall, this study provides a comprehensive single-cell atlas of the developing human lung, outlining the temporal and spatial complexities of cell lineage development and benchmarks fetal lung cultures from hPSC differentiations to similar developmental window.
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Project description:Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity [scRNAseq-hPSC]
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Project description:Fetal lung samples at 12–20 post conception week (pcw) from the HDBR, up to 0.5cm3 in size, were embedded in OCT and flash-frozen in dry-ice cooled isopentane. Twelve-micron cryosections were cut onto Visium slides, haematoxylin and eosin stained and imaged at 20X magnification on a Hamamatsu Nanozoomer 2.0 HT Brightfield. These were then further processed according to the 10X Genomics Visium protocol, using a permeabilization time of 18 min for 12–17 pcw samples and 24 min for 19 pcw and older samples. Images were exported as tiled tiffs for analysis. Dual-indexed libraries were prepared as in the 10X Genomics protocol, pooled at 2.25 nM and sequenced in 4 samples per Illumina Novaseq SP flow cell with read lengths of 28 bp for R1, 10 bp for i7 index, 10 bp for i5 index, 90 bp for R2.
2022-01-27 | E-MTAB-11265 | biostudies-arrayexpress
Project description:A high-resolution single-cell multiomic atlas of the human fetal lung - Visium
| PRJEB54910 | ENA
Project description:As part of the Human Cell Atlas we will study fetal tissue.
| EGAS00001002553 | EGA