Single-cell RNA sequencing identifies diverse roles of epithelial cells in idiopathic pulmonary fibrosis.
JCI Insight
; 1(20): e90558, 2016 12 08.
Article
em En
| MEDLINE
| ID: mdl-27942595
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease characterized by airway remodeling, inflammation, alveolar destruction, and fibrosis. We utilized single-cell RNA sequencing (scRNA-seq) to identify epithelial cell types and associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis of normal human lung epithelial cells defined gene expression patterns associated with highly differentiated alveolar type 2 (AT2) cells, indicated by enrichment of RNAs critical for surfactant homeostasis. In contrast, scRNA-seq of IPF cells identified 3 distinct subsets of epithelial cell types with characteristics of conducting airway basal and goblet cells and an additional atypical transitional cell that contributes to pathological processes in IPF. Individual IPF cells frequently coexpressed alveolar type 1 (AT1), AT2, and conducting airway selective markers, demonstrating "indeterminate" states of differentiation not seen in normal lung development. Pathway analysis predicted aberrant activation of canonical signaling via TGF-ß, HIPPO/YAP, P53, WNT, and AKT/PI3K. Immunofluorescence confocal microscopy identified the disruption of alveolar structure and loss of the normal proximal-peripheral differentiation of pulmonary epithelial cells. scRNA-seq analyses identified loss of normal epithelial cell identities and unique contributions of epithelial cells to the pathogenesis of IPF. The present study provides a rich data source to further explore lung health and disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Análise de Sequência de RNA
/
Células Epiteliais
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Fibrose Pulmonar Idiopática
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
JCI Insight
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos