Single-Cell Transcriptomic Analysis Identifies a Translation/RBP-Related Fibroblast Signature for Drug Repurposing in Idiopathic Pulmonary Fibrosis
- 1Center for Biological Science and Technology, Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Guangdong Zhuhai-Macao Joint Biotech Laboratory, Department of Biology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai 519087, China
- 2School of Pharmacy, Mudanjiang Medical University, Mudanjiang 157011, China
Abstract
Idiopathic pulmonary fibrosis (IPF) is characterized by persistent fibroblast activation and excessive extracellular matrix deposition. However, transcriptional heterogeneity associated with translation- and RNA-binding protein (RBP)-related processes within IPF fibroblasts remains incompletely characterized. Here, we analyzed two independent human IPF single-cell RNA-sequencing cohorts to identify fibroblast states that differed in Translation/RBP-related transcriptional programs while sharing high fibrotic output. Donor-paired pseudobulk analysis in GSE136831 identified a transcriptional signature distinguishing these states, and genes showing consistent directional changes in the independent GSE135893 cohort were retained to derive a cross-cohort signature. Reverse-connectivity analysis across CLUE, L1000CDS2, and iLINCS was then used to prioritize compounds predicted to transcriptionally oppose this signature. Candidate compounds were subsequently evaluated in transforming growth factor-β1 (TGF-β1)-stimulated human fetal lung fibroblasts (HFL-1), with cell viability, α-smooth muscle actin (α-SMA), and collagen I used for initial phenotypic assessment. PP-1, PK-11195, dabrafenib, GSK-1059615, and dasatinib reduced both profibrotic markers within the tested concentration ranges, identifying them as candidates for further investigation. Together, these findings define a cross-cohort Translation/RBP-related fibroblast signature in IPF and support its use as a transcriptome-guided strategy for prioritizing compounds with antifibrotic phenotypic activity.
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BibTeX
@article{qiao2026singlecell,
title = {{Single-Cell Transcriptomic Analysis Identifies a Translation/RBP-Related Fibroblast Signature for Drug Repurposing in Idiopathic Pulmonary Fibrosis}},
author = {Yongkang Qiao and Chaoyue Cui and Yanhong Han and Xinxin Tang and Zhen Yang and Chuang Ge},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = oct,
doi = {10.3390/ijms27219736},
url = {https://www.mdpi.com/1422-0067/27/21/9736},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-Cell Transcriptomic Analysis Identifies a Translation/RBP-Related Fibroblast Signature for Drug Repurposing in Idiopathic Pulmonary Fibrosis
AU - Yongkang Qiao
AU - Chaoyue Cui
AU - Yanhong Han
AU - Xinxin Tang
AU - Zhen Yang
AU - Chuang Ge
PY - 2026
DA - 2026/10/30
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219736
UR - https://www.mdpi.com/1422-0067/27/21/9736
AB - Idiopathic pulmonary fibrosis (IPF) is characterized by persistent fibroblast activation and excessive extracellular matrix deposition. However, transcriptional heterogeneity associated with translation- and RNA-binding protein (RBP)-related processes within IPF fibroblasts remains incompletely characterized. Here, we analyzed two independent human IPF single-cell RNA-sequencing cohorts to identify fibroblast states that differed in Translation/RBP-related transcriptional programs while sharing high fibrotic output. Donor-paired pseudobulk analysis in GSE136831 identified a transcriptional signature distinguishing these states, and genes showing consistent directional changes in the independent GSE135893 cohort were retained to derive a cross-cohort signature. Reverse-connectivity analysis across CLUE, L1000CDS2, and iLINCS was then used to prioritize compounds predicted to transcriptionally oppose this signature. Candidate compounds were subsequently evaluated in transforming growth factor-β1 (TGF-β1)-stimulated human fetal lung fibroblasts (HFL-1), with cell viability, α-smooth muscle actin (α-SMA), and collagen I used for initial phenotypic assessment. PP-1, PK-11195, dabrafenib, GSK-1059615, and dasatinib reduced both profibrotic markers within the tested concentration ranges, identifying them as candidates for further investigation. Together, these findings define a cross-cohort Translation/RBP-related fibroblast signature in IPF and support its use as a transcriptome-guided strategy for prioritizing compounds with antifibrotic phenotypic activity.
SN - 1422-0067
ER -