Journal article
Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD
Respiratory research, Vol.22(1), pp.100-13
04/06/2021
DOI: 10.1186/s12931-021-01675-2
PMID: 33823868
Abstract
Whole lung tissue transcriptomic profiling studies in chronic obstructive pulmonary disease (COPD) have led to the identification of several genes associated with the severity of airflow limitation and/or the presence of emphysema, however, the cell types driving these gene expression signatures remain unidentified.
To determine cell specific transcriptomic changes in severe COPD, we conducted single-cell RNA sequencing (scRNA seq) on n = 29,961 cells from the peripheral lung parenchymal tissue of nonsmoking subjects without underlying lung disease (n = 3) and patients with severe COPD (n = 3). The cell type composition and cell specific gene expression signature was assessed. Gene set enrichment analysis (GSEA) was used to identify the specific cell types contributing to the previously reported transcriptomic signatures.
T-distributed stochastic neighbor embedding and clustering of scRNA seq data revealed a total of 17 distinct populations. Among them, the populations with more differentially expressed genes in cases vs. controls (log fold change >|0.4| and FDR = 0.05) were: monocytes (n = 1499); macrophages (n = 868) and ciliated epithelial cells (n = 590), respectively. Using GSEA, we found that only ciliated and cytotoxic T cells manifested a trend towards enrichment of the previously reported 127 regional emphysema gene signatures (normalized enrichment score [NES] = 1.28 and = 1.33, FDR = 0.085 and = 0.092 respectively). Among the significantly altered genes present in ciliated epithelial cells of the COPD lungs, QKI and IGFBP5 protein levels were also found to be altered in the COPD lungs.
scRNA seq is useful for identifying transcriptional changes and possibly individual protein levels that may contribute to the development of emphysema in a cell-type specific manner.
Details
- Title: Subtitle
- Single cell RNA sequencing identifies IGFBP5 and QKI as ciliated epithelial cell genes associated with severe COPD
- Creators
- Xiuying Li - University of PittsburghGuillaume Noell - Centro de Investigación Biomédica en Red de Enfermedades RespiratoriasTracy Tabib - University of PittsburghAlyssa D Gregory - University of PittsburghHumberto E Trejo Bittar - University of PittsburghRavi Vats - University of PittsburghTomasz W Kaminski - University of PittsburghJohn Sembrat - University of PittsburghMark E Snyder - University of PittsburghDivay Chandra - University of PittsburghKong Chen - University of PittsburghChunbin Zou - University of PittsburghYingze Zhang - University of PittsburghPrithu Sundd - University of PittsburghJohn F McDyer - University of PittsburghFrank Sciurba - University of PittsburghMauricio Rojas - University of PittsburghRobert Lafyatis - University of PittsburghSteve D Shapiro - University of PittsburghRosa Faner - Centro de Investigación Biomédica en Red de Enfermedades RespiratoriasToru Nyunoya - University of Pittsburgh
- Resource Type
- Journal article
- Publication Details
- Respiratory research, Vol.22(1), pp.100-13
- DOI
- 10.1186/s12931-021-01675-2
- PMID
- 33823868
- ISSN
- 1465-993X
- eISSN
- 1465-993X
- Grant note
- 19TPA34830061 / American Heart Association R01 HL142997 / NHLBI NIH HHS U01 HL145550 / NHLBI NIH HHS R01 HL125435 / NHLBI NIH HHS R01 HL149719 / NHLBI NIH HHS CP16/00039 / Instituto de Salud Carlos III R01 HL128297 / NHLBI NIH HHS R01 HL153400 / NHLBI NIH HHS HL149719 / NHLBI NIH HHS PI17/00369 / Instituto de Salud Carlos III
- Language
- English
- Date published
- 04/06/2021
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985214172902771
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