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

Carraro, Gianni; Mulay, Apoorva; Yao, Changfu; Mizuno, Takako; Konda, Bindu; Petrov, Martin; Lafkas, Daniel; Arron, Joseph R.; Hogaboam, Cory M.; Chen, Peter; Jiang, Dianhua; Noble, Paul W.; Randell, Scott H.; McQualter, Jonathan L.; Stripp, Barry R.

doi:10.1164/rccm.201904-0792oc

Cited by 109 publications

(102 citation statements)

References 28 publications

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“…A Brown-Forsythe and Welsh ANOVA were used for cytokine and chemokine NELF and NLF analyses. Analyses were completed in GraphPad Prism, and significance was determined to be present when P was less than 0.1, which was based on the use of clinical data with a relatively small N ( 41 , 46 ).…”

Section: Methodsmentioning

confidence: 99%

Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial

Rebuli

Glista-Baker

Hoffman³

et al. 2021

Am J Respir Cell Mol Biol

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Section: Methodsmentioning

confidence: 99%

Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial

Rebuli

Glista-Baker

Hoffman³

et al. 2021

Am J Respir Cell Mol Biol

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“…Basal cells are the major stem cells in the human airways that self-renew and can give rise to all other cell types of the airways ( 33 ). scRNAseq studies have identified various clusters of basal cells in humans, that might differ in their ability to function as stem cells ( 20 , 22 , 28 ). Carraro et al reported a sub-population of CD66 + secretory cell primed basal (SPB) cells, that share a molecular signature with basal cells recovered from fibrotic lung tissue ( 28 ).…”

Section: Diversity Of Lung Cell Types and Regulatory Mechanisms Durinmentioning

confidence: 99%

“…scRNAseq studies have identified various clusters of basal cells in humans, that might differ in their ability to function as stem cells ( 20 , 22 , 28 ). Carraro et al reported a sub-population of CD66 + secretory cell primed basal (SPB) cells, that share a molecular signature with basal cells recovered from fibrotic lung tissue ( 28 ). SPB cells from IPF were enriched in CEACAM6 expression and could be distinguished from normal SPB cells by their gene signature.…”

Section: Diversity Of Lung Cell Types and Regulatory Mechanisms Durinmentioning

confidence: 99%

“…However, their differentiation into airway rather than alveolar phenotypes potentially accounts for the dysplastic structures observed in fibrotic lung tissues ( 36 ). These structural defects are considered to be secondary to epithelial progenitor cell dysfunction and defective epithelial-mesenchymal signaling ( 28 ).…”

Section: Diversity Of Lung Cell Types and Regulatory Mechanisms Durinmentioning

confidence: 99%

“…scRNAseq studies have vastly increased our understanding of cell types resident in the distal lung and also highlighted differences in cell populations/states between healthy and IPF tissue ( 12 – 15 , 20 , 25 , 28 , 44 , 45 ). Recent efforts aimed at extending these insights to a better understanding of mechanisms for the local and temporal disease progression or leveraging scRNAseq analysis to progress disease biomarker identification ( 27 , 46 ).…”

Section: New Insights From Scrnaseq Studies Into Disease Progression mentioning

confidence: 99%

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Insights Into Development and Progression of Idiopathic Pulmonary Fibrosis From Single Cell RNA Studies

2020

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Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited therapeutic options. The current model suggests that chronic or repetitive “micro-injuries” of the alveolar epithelium lead to activation and proliferation of fibroblasts and excessive extracellular matrix (ECM) deposition. Disruption of alveolar type II (ATII) epithelial cell homeostasis and the characteristics of mesenchymal cell populations in IPF have received particular attention in recent years. Emerging data from single cell RNA sequencing (scRNAseq) analysis shed novel light on alterations in ATII cell progenitor dysfunction and the diversity of mesenchymal cells within the fibrotic lung. Within this minireview, we summarize the data from most recent human scRNAseq studies. We aim to collate the current knowledge on cellular plasticity and heterogeneity in the development and progression of IPF, effects of drug treatment on transcriptional changes. Finally, we provide a brief outlook on future challenges and promises for large scale sequencing studies in the development of novel therapeutics for IPF.

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Insights gained in the pathology of lung disease through single‐cell transcriptomics

Carraro

Stripp

2022

The Journal of Pathology

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The human lung is a relatively quiescent organ in the normal healthy state but contains stem/progenitor cells that contribute to normal tissue maintenance and either repair or remodeling in response to injury and disease. Maintenance or repair lead to proper restoration of functional lung tissue and maintenance of physiological functions, with remodeling resulting in altered structure and function that is typically associated with disease. Knowledge of cell types contributing to lung tissue maintenance and repair/remodeling have largely relied on mouse models of injury‐repair and lineage tracing of local progenitors. Therefore, many of the functional alterations underlying remodeling in human lung disease have remained poorly defined. However, the advent of advanced genomics approaches to define the molecular phenotype of lung cells at single‐cell resolution has paved the way for rapid advances in our understanding of cell types present within the normal human lung and changes that accompany disease. Here we summarize recent advances in our understanding of disease‐related changes in the molecular phenotype of human lung epithelium that have emerged from single‐cell transcriptomic studies. We focus attention on emerging concepts of epithelial transitional states that characterize the pathological remodeling that accompanies chronic lung diseases, including idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, and asthma. Concepts arising from these studies are actively evolving and require corroborative studies to improve our understanding of disease mechanisms. Whenever possible, we highlight opportunities for providing a unified nomenclature in this rapidly advancing field of research. © 2022 The Pathological Society of Great Britain and Ireland.

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

Cited by 109 publications

References 28 publications

Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial

Electronic-Cigarette Use Alters Nasal Mucosal Immune Response to Live-attenuated Influenza Virus. A Clinical Trial

Insights Into Development and Progression of Idiopathic Pulmonary Fibrosis From Single Cell RNA Studies

Insights gained in the pathology of lung disease through single‐cell transcriptomics

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