Abstract
We present a multiomic cell atlas of human lung development that combines single cell RNA and ATAC sequencing, high throughput spatial transcriptomics and single cell imaging. Coupling single cell methods with spatial analysis has allowed a comprehensive cellular survey of the epithelial, mesenchymal, endothelial and erythrocyte/leukocyte compartments from 5-22 post conception weeks. We identify new cell states in all compartments. These include developmental-specific secretory progenitors and a new subtype of neuroendocrine cell related to human small cell lung cancer. Our datasets are available through our web interface (https://lungcellatlas.org). Finally, to illustrate its general utility, we use our cell atlas to generate predictions about cell-cell signalling and transcription factor hierarchies which we test using organoid models.
Highlights
Spatiotemporal atlas of human lung development from 5-22 post conception weeks identifies 144 cell types/states.
Tracking the developmental origins of multiple cell compartments, including new progenitor states.
Functional diversity of fibroblasts in distinct anatomical signalling niches.
Resource applied to interrogate and experimentally test the transcription factor code controlling neuroendocrine cell heterogeneity and the origins of small cell lung cancer.
Competing Interest Statement
In the past 3 years, SAT has worked as a consultant for Genentech, Roche and Transition Bio, is a remunerated member of the scientific advisory boards of Biogen, GlaxoSmithKline, Foresite Labs and Qiagen and is an equity holder of Transition Bio. ZKT has received consulting fees from Synteny Biotechnologies for activities unrelated to this work.
Footnotes
Added in situ staining and computational analyses
https://github.com/brianpenghe/python-genomics/tree/master/Human_fetal_lung_cell_atlas_2022