Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity [Xenium]
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ABSTRACT:
PROVIDER: PRJNA1102393 | ENA |
REPOSITORIES: ENA
Similar Datasets
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-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.
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Project description:Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity [Visium]
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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:As part of the Human Cell Atlas we will study fetal tissue.
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Project description:Studying human fetal lungs can inform how developmental defects and disease states alter the function of the lungs. Here, we sequenced >150,000 single cells from 19 healthy human pseudoglandular fetal lung tissues ranging between gestational weeks 10-19. We capture dynamic developmental trajectories from progenitor cells that express abundant levels of the cystic fibrosis conductance transmembrane regulator (CFTR). These cells give rise to multiple specialized epithelial cell types. Combined with spatial transcriptomics, we show temporal regulation of key signalling pathways that may drive the temporal and spatial emergence of specialized epithelial cells including ciliated and pulmonary neuroendocrine cells. Finally, we show that human pluripotent stem cell-derived fetal lung models contain CFTR-expressing progenitor cells that capture similar lineage developmental trajectories as identified in the native tissue. 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 human pluripotent stem cell differentiations to similar developmental window.
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