Single-Cell Reconstruction of Human Basal Cell Diversity in Normal and Idiopathic Pulmonary Fibrosis Lungs.

American Journal of Respiratory and Critical Care Medicine
G. CarraroBarry R Stripp

Abstract

Rationale: Declining lung function in patients with interstitial lung disease is accompanied by epithelial remodeling and progressive scarring of the gas-exchange region. There is a need to better understand the contribution of basal cell hyperplasia and associated mucosecretory dysfunction to the development of idiopathic pulmonary fibrosis (IPF).Objectives: We sought to decipher the transcriptome of freshly isolated epithelial cells from normal and IPF lungs to discern disease-dependent changes within basal stem cells.Methods: Single-cell RNA sequencing was used to map epithelial cell types of the normal and IPF human airways. Organoid and air-liquid interface cultures were used to investigate functional properties of basal cell subtypes.Measurements and Main Results: We found that basal cells included multipotent and secretory primed subsets in control adult lung tissue. Secretory primed basal cells include an overlapping molecular signature with basal cells obtained from the distal lung tissue of IPF lungs. We confirmed that NOTCH2 maintains undifferentiated basal cells and restricts basal-to-ciliated differentiation, and we present evidence that NOTCH3 functions to restrain secretory differentiation.Conclusions: Basal cell...Continue Reading

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Citations

Oct 24, 2020·American Journal of Respiratory Cell and Molecular Biology·Meghan E RebuliIlona Jaspers
Oct 26, 2020·Cell Stem Cell·Finn J HawkinsDarrell N Kotton
Oct 1, 2020·American Journal of Physiology. Lung Cellular and Molecular Physiology·Nir NeumarkNaftali Kaminski
Sep 12, 2020·American Journal of Respiratory and Critical Care Medicine·Oliver EickelbergPatricia J Sime
Feb 18, 2021·American Journal of Respiratory Cell and Molecular Biology·Daniel Lafkas
Jan 15, 2021·American Journal of Respiratory Cell and Molecular Biology·Manish BodasMatthew S Walters
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Datasets Mentioned

BETA
GSE143705

Methods Mentioned

BETA
scraping
fluorescence-activated cell sorting
protein folding
flow cytometry
scRNAseq
PCA

Software Mentioned

Slingshot
Zen Blue
Destiny

Related Concepts

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