Dataset Information

Type I interferon–activated myeloid states are associated with less fibrotic stages in idiopathic pulmonary fibrosis

ABSTRACT: Early immune processes in idiopathic pulmonary fibrosis (IPF) are poorly defined. Here, we integrate single cell transcriptomics of lung digest and bronchoalveolar-lavaged cells (n=108 patients), subcellular-resolution tissue spatial transcriptomics, and single-cell phospho-CyTOF of blood cells to define myeloid states associated with early stages of fibrosis. Two distinct myeloid gene transcriptional programmes are increased in IPF compared to non-diseased controls - type I interferon-activated and fibrotic remodelling programme. At cell, organ and patient levels, cell types with increased type I interferon-activated programme (FABP4hi alveolar macrophages, classical monocytes, interstitial macrophages and non-classical monocytes) are associated with architecturally better-preserved lung tissue, the alveolar barrier and less fibrotic lung, or less severe disease. Circulating monocytes exhibited heightened type I interferon responsiveness that inversely correlated with severity of clinical disease. Our findings show that myeloid cells with increased type I interferon-activated gene programmes are associated with less fibrotic stages of IPF.

ORGANISM(S): Homo sapiens

PROVIDER: GSE292589 | GEO | 2026/07/10

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:As a group, fibroproliferative disorders of the lung, liver, kidney, heart, vasculature and integument are common, progressive and refractory to therapy. They can emerge following toxic insults, but are frequently idiopathic. Their enigmatic propensity to resist therapy and progress to organ failure has focused attention on the myofibroblast – the primary effector of the fibroproliferative response. A central unanswered question is whether these myofibroblasts have acquired a distinct pathological phenotype - or whether they are normal myofibroblasts with a pathological phenotype that depends upon residing in a sea of pro-fibrotic cytokines and an abnormal extracellular matrix. Using a systems approach to study this question in a prototype fibrotic disease, Idiopathic Pulmonary Fibrosis (IPF); here we show organized changes in the gene expression pathway of primary lung myofibroblasts that persist for up to 9 sub-cultivations in vitro. When comparing IPF and control myofibroblasts in a 3-dimensional type I collagen matrix, more genes differed at the level of ribosome recruitment than at the level of transcript abundance, indicating pathological translational control as a major characteristic of IPF myofibroblasts. To determine the effect of matrix state on translational control, myofibroblasts were permitted to contract the matrix. Ribosome recruitment in control myofibroblasts was relatively stable. In contrast, IPF cells manifested large alterations in the ribosome recruitment pattern. Pathological studies suggest an epithelial origin for IPF myofibroblasts through the epithelial to mesenchymal transition (EMT). In accord with this, we found systems-level indications for TGF?b -driven EMT as one source of IPF myofibroblasts. Keywords: cell type comparison Comparison of lung myofibroblasts from patients with Idiopatic Pulmonary Fibrosis (IPF, 6 donors) to control (6 donors) in contractile and non-contractile matrices using both total and polyribosomal RNA

Dataset Information

Type I interferon–activated myeloid states are associated with less fibrotic stages in idiopathic pulmonary fibrosis

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets