CD248 and integrin alpha-8 are candidate markers for differentiating lung fibroblast subtypes

Abstract

Background: Lung fibrosis is a serious life-threatening condition whose manifestation varies according to the localization and characteristics of fibroblasts, which are considered heterogeneous. Therefore, to better understand the pathology and improve diagnosis and treatment of this disease, it is necessary to elucidate the nature of this heterogeneity and identify markers for the accurate classification of human lung fibroblast subtypes. Methods: We characterized distinct mouse lung fibroblast subpopulations isolated by fluorescence-activated cell sorting (FACS) and performed microarray analysis to identify molecular markers that could be useful for human lung fibroblast classification. Based on the expression of these markers, we evaluated the fibroblast-like cell subtype localization in normal human lung samples and lung samples from patients with idiopathic pulmonary fibrosis (IPF). Results: Mouse lung fibroblasts were classified into Sca-1 high fibroblasts and Sca-1 low fibroblasts by in vitro biological analyses. Through microarray analysis, we demonstrated CD248 and integrin alpha-8 (ITGA8) as cell surface markers for Sca-1 high fibroblasts and Sca-1 low fibroblasts, respectively. In mouse lungs, Sca-1 high fibroblasts and Sca-1 low fibroblasts were localized in the collagen fiber-rich connective tissue and elastic fiber-rich connective tissue, respectively. In normal human lungs and IPF lungs, two corresponding major fibroblast-like cell subtypes were identified: CD248 high ITGA8 low fibroblast-like cells and CD248 low ITGA8 high fibroblast-like cells, localized in the collagen fiber-rich connective tissue and in the elastic fiber-rich connective tissue, respectively. Conclusion: CD248 high ITGA8 low fibroblast-like cells and CD248 low ITGA8 high fibroblast-like cells were localized in an almost exclusive manner in human lung specimens. This human lung fibroblast classification using two cell surface markers may be helpful for further detailed investigations of the functions of lung fibroblast subtypes, which can provide new insights into lung development and the pathological processes underlying fibrotic lung diseases.

Outgrowth of erlotinib-resistant subpopulations recapitulated in patient-derived lung tumor spheroids and organoids

“…For example, Fig 4 shows significantly greater growth (as total spheroid area and number) in 0 μM than in 10 μM erlotinib. [37]. This aggregation is…”

Fibroblasts as a Biological Marker for Curative Resection in Pancreatic Ductal Adenocarcinoma

“…There was no significant difference in either DFS (p = 0.925) or OS (p = 0.492) between αSMA-high/FAPα-low and αSMA-low/FAPα-high groups ( Figure 3D,E). We also performed an analysis using markers CD248 and ITGA8, which were reported as markers to distinguish lung fibroblast subtypes [12], and there was also no significant survival difference ( Figure S1). Given these results that failed to reproduce those of previous studies, we concluded that fibroblast subtypes were indistinguishable when utilizing the gene expressions of fibroblast surface markers in PDAC bulk tumors alone.…”

Stromal Heterogeneity in the Proliferative EndometrialFunctionalis- A single-cell approach

“…surrounding vasculature) and vital in the regulation of tissue remodeling and homeostasis. The BMP7+ population had genes involved in myofibroblast differentiation, epithelial mesenchymal transition (EMT) and in TGFβ1-WNT signaling (PRSS23, ITGA8, BMP7, ITM2A and ARHGAP29) (15)(16)(17)(18). We hypothesize these three stromal clusters (ACTA+, ECM and BMP7+) represent stromal subtypes active in ECM breakdown, remodeling and organization which are important processes during proliferation, tissue repair and regeneration occurring in the endometrium, during, and after menstruation.…”