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Tissue-based Gene Expression as Potential Biomarkers for IBD Course.

ABSTRACT: Inflammatory bowel diseases (IBDs) are highly heterogeneous in disease phenotype, behavior, and response to therapy. Diagnostic and therapeutic decisions in IBD are based primarily on clinical and endoscopic severity and histopathologic analysis of intestinal biopsies. With this approach, however, only a minority of patients experience durable remission. This may be due to substantial heterogeneity in disease pathogenicity that is not accounted for by current classification systems. Patients can present with similar clinical and endoscopic severity and receive similar therapy but show divergent response ranging from mucosal/transmural healing to nonresponse. Using mucosal biopsy samples that are already obtained as part of the clinical practice to support the diagnosis and state-of-the-art high throughput sequencing approaches can detect the widest range in host gene expression in the actual lining of the affected gut. These analyses can better dissect disease heterogeneity and guide potential treatment response. Here we review studies that use gut tissue-based gene expression profiles to predict disease outcome in IBD.

SUBMITTER: Haberman Y

PROVIDER: S-EPMC7500516 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Tissue-based Gene Expression as Potential Biomarkers for IBD Course.

Haberman Yael Y

Inflammatory bowel diseases 20200901 10

Inflammatory bowel diseases (IBDs) are highly heterogeneous in disease phenotype, behavior, and response to therapy. Diagnostic and therapeutic decisions in IBD are based primarily on clinical and endoscopic severity and histopathologic analysis of intestinal biopsies. With this approach, however, only a minority of patients experience durable remission. This may be due to substantial heterogeneity in disease pathogenicity that is not accounted for by current classification systems. Patients can ...[more]

PMID: 32812640

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Project description:PurposeIncreasing evidence suggests myopia is not a simple refractive error, many other factors might also be involved. Here, we assessed myopic and normal corneas' gene expression profiles to identify possible diagnostic and therapeutic biomarkers for myopia.Materials and methodsWe obtained the expression profile of ten patients and seven normal control samples from the GSE112155 and GSE151631 datasets based on the Gene Expression Omnibus (GEO) database. We used the "limma" R package to determine the differentially expressed genes (DEGs) between myopic and normal corneas. Weighted gene co-expression network analysis (WGCNA) was used to identify critical co-expressed modules related to myopia, and enrichment analyses were used to annotate the function of genes encompassed in the compulsory module. We also validated these findings in two external datasets (GSE24641 and GSE136701).ResultsWe identified that the DEGs were significantly enriched in ultraviolet (UV) response, TNF-α signaling via NFκB, Angiogenesis, Myogenesis pathways, etc. We used 2095 genes to construct the co-expression gene modules and found five interesting modules because the eigengene expression of these modules was significantly differentially expressed between myopic and normal corneas. Notably, the enrichment analysis found that the genes encompassed in lightgreen module were significantly enriched in immune-related pathways. These findings were proved by subsequent analysis based on Xcell software. We found the component of B cells, CD4+ memory T cells, CD8+ central memory T cells, plasmacytoid dendritic cells, T helper 2 (Th2) cells, regulatory T cells (Tregs), etc. were significantly increased in myopic corneas, while CD8+ T cells, CD4+ T central memory cells, natural killer T (NKT) cells, and T helper 1 (Th1) cells were significantly decreased.ConclusionOur findings identified some markers that might detect diagnosis and treatment for myopia from cornea aspect. Future studies are warranted to verify the functional role of immune-related pathways in cornea during the pathogenesis or progression of myopia.

Project description:IntroductionMesenchymal stem cells have been increasingly used for cell-based therapies. Adipose-derived stem/stromal cells (ASCs) from the stromal vascular fraction (SVF) of fat tissue are a particularly attractive option for cell based therapy given their accessibility and relative abundance. However, their application in both clinical and basic science investigations is complicated by the isolation of differentiable cells within the SVF. Current enrichment strategies, such as monolayer passaging and surface marker-based sorting, can be time-consuming or overly stringent. Ideally, a population of cells with great regenerative capacity could be isolated with high yields so that extensive in vitro manipulation is not necessary. The objective of this study was to determine whether SVF cells sorted based on expression of alkaline phosphatase liver/bone/kidney (ALPL) resulted in populations with increased osteogenic differentiation potential.MethodsSVF samples were obtained from four, human donors and processed to isolate initial, heterogeneous cell populations. These SVF cells underwent a four day osteogenic priming period, after which they were treated with a fluorescent, oligodeoxynucleotide molecular beacon probe specific for ALPL mRNA. Cells were separated into positive and negative groups using fluorescence-activated cell sorting (FACS) then differentiated down the osteogenic lineage. Differentiation was assessed by measuring calcified matrix production in each sample.ResultsCells positive for ALPL expression (ALPL+) represented approximately 34% of the gated population, while cells negative for ALPL expression (ALPL-) represented approximately 18%. ALPL+?cells produced 3.7-fold and 2.1-fold more calcified matrix than ALPL- and unsorted SVF cells, respectively, indicating a significant improvement in osteogenic differentiation. Further, ALPL+?cells showed increases in metabolite production for both adipogenesis and chondrogenesis, suggesting that the enrichment process yields an enhanced multipotent phenotype. Osteogenic differentiation response and cell yields for ALPL+?cells were markedly improved over surface marker-sorted samples.ConclusionThis study demonstrates a novel method to enrich heterogeneous SVF cells for increased osteogenic potential. The procedure requires less time and results in higher yields of therapeutically useful cells than other existing approaches. Gene expression-based sorting of MSCs is a potentially paradigm-shifting approach that could benefit applications spanning from basic science to clinical therapy.

Dataset Information

Tissue-based Gene Expression as Potential Biomarkers for IBD Course.

Publications

Tissue-based Gene Expression as Potential Biomarkers for IBD Course.

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