Dysregulated Polycomb Repressive Complex 2 contributes to chronic obstructive pulmonary disease by rewiring stem cell fate
Year: 2022
Type: article
Abstract: Aberrant lung cell differentiation is a hallmark of many lung diseases including chronic obstructive pulmonary disease (COPD). The EZH2-containing Polycomb Repressive Complex 2 (PRC2) regulates embryonic lung stem cell fate, but its role in adult lung is obscure. Histological analysis of patient tissues revealed that loss of PRC2 activity was correlated with aberrant bronchiolar cell differentiation in COPD lung. Histological and single-cell RNA-sequencing analyses showed that loss of EZH2 in mouse lung organoids led to lowered self-renewal capability, increased squamous morphological development, and marked shifts in progenitor cell populations. Evaluation of in vivo models revealed that heterozygosity of Ezh2 in mice with ovalbumin-induced lung inflammation led to epithelial cell differentiation patterns similar to those in COPD lung. We also identified cystathionine-β-synthase as a possible upstream factor for PRC2 destabilization. Our findings suggest that PRC2 is integral to facilitating proper lung stem cell differentiation in humans and mice.
Source: Stem Cell Reports
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,800
Funders: American Cancer Society, V Foundation for Cancer Research, Israel National Road Safety Authority, National Institutes of Health, Markey Cancer Center, University of Kentucky, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences
Awards: G1111225398, Training Grant in Molecular Mechanisms of Toxicity, Defining epigenetic vulnerabilities of subtype-specific lung cancers, G1605188729, Targeting epigenetic heterogeneity to improve lung cancer immunotherapy response, G3908267398, G532979230, Bronchiolar Dysplasia in COPD is Governed by Loss of Polycomb Repressive Complex 2, G7661955760, University of Kentucky Markey Cancer Center – Cancer Center Support Grant, University of Kentucky Center for Cancer Metabolism
OpenAlex ID: W4311539899