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| Status |
Public on Jun 04, 2024 |
| Title |
Early human fetal lung atlas reveals the temporal dynamics of epithelial cell plasticity [Visium] |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
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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| Overall design |
Two archived FFPE fetal lung tissues (GW 15 and 18) were freshly sectioned and analyzed through 10X Visium.
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| Contributor(s) |
Quach H, Farrell S, Wu MJ, Kanagarajah K, Leung JW, Xu X, Kallurkar P, Turinsky AL, Bear CE, Ratjen F, Kalish B, Goyal S, Moreas TJ, Wong AP |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Apr 19, 2024 |
| Last update date |
Jun 05, 2024 |
| Contact name |
Amy Wong |
| E-mail(s) |
apwong@sickkids.ca
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| Phone |
4168139334
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| Organization name |
The Hospital for Sick Children
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| Department |
Developmental & Stem Cell Biology
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| Street address |
686 Bay Street, Toronto
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| City |
Toronto |
| State/province |
Ontario |
| ZIP/Postal code |
M5G 0A4 |
| Country |
Canada |
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| Platforms (1) |
| GPL34284 |
Illumina NovaSeq X Plus (Homo sapiens) |
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| Samples (2) |
| GSM8217624 |
FFPE archived fetal lung tissue GW15; Visium |
| GSM8217625 |
FFPE archived fetal lung tissue GW18; Visium |
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| Relations |
| BioProject |
PRJNA1102342 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE264398_RAW.tar |
194.3 Mb |
(http)(custom) |
TAR (of CSV, JPG, JSON, MTX, PNG, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
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