Gene expression profiles in mesenchymal stromal cells from bone marrow, adipose tissue and lung tissue of COPD patients and controls

Abstract

Background Chronic obstructive pulmonary disease (COPD) is characterized by irreversible lung tissue damage. Novel regenerative strategies are urgently awaited. Cultured mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental models of COPD, but differences between sources may impact on their potential use in therapeutic strategies in patients. Aim To assess the transcriptome of lung-derived MSCs (LMSCs), bone marrow-derived MSCs (BM-MSC) and adipose-derived MSCs (AD-MSCs) from COPD patients and non-COPD controls. Methods We studied differences in gene expression profiles between the MSC-subtypes, as well as between COPD and control using RNA sequencing (RNA-seq). Results We show that besides heterogeneity between donors, MSCs from different sources have strongly divergent gene signatures. The growth factors FGF10 and HGF were predominantly expressed in LMSCs. MSCs from all sources displayed altered expression profiles in COPD, with most pronounced significantly up- and downregulated genes in MSCs from adipose tissue. Pathway analysis revealed that the most differentially expressed genes in COPD-derived AD-MSCs are involved in extracellular matrix (ECM) binding and expression. In LMSCs, the gene that differed most strongly between COPD and control was CSGALNACT1, an ECM modulating gene. Conclusion Autologous MSCs from COPD patients display abnormalities with respect to their transcriptome, which were surprisingly most profound in MSCs from extrapulmonary sources. LMSCs may be optimally equipped for lung tissue repair because of the expression of specific growth factor genes.

Analysis and Validation of Critical Signatures and Immune Cell Infiltration Characteristics in Doxorubicin-Induced Cardiotoxicity by Integrating Bioinformatics and Machine Learning

“… 46 According to a recent study, CSGALNACT1 was found to have a notable upregulation in lung-derived mesenchymal stem cells (LMSCs) from emphysema patients, which can regulate extracellular matrix (ECM), but the specific function remains unclear. 47 Significantly, chondroitin sulfate (CS) is a natural macromolecule catalyzed by CSGALNACT1 and a major component of the extracellular matrix. 48 Another study published recently showed that abnormal accumulation of chondroitin sulfate glycosaminoglycans led to cardiac fibrosis.…”

Analysis and validation of critical signatures and immune cell infiltration characteristics in doxorubicin-induced cardiotoxicity by integrating bioinformatics and machine learning

“…Previous microarray studies have indicated that CSGALNACT1 is a prognostic biomarker in multiple myeloma [41]. According to a recent study, CSGALNACT1 was found to have a notable upregulation in lung-derived mesenchymal stem cells (LMSCs) from emphysema patients, which can regulate extracellular matrix (ECM), but the speci c function remains unclear [42]. Signi cantly, chondroitin sulfate (CS) is a natural macromolecule catalyzed by CSGALNACT1 and a major component of the extracellular matrix [43].…”