Biology subjects

Huan, B.

Publications and source records attributed to Huan, B..

3 recordsLinked to original sources

bioRxiv2026

Transcriptome-wide Differential Expression and Splicing in Inflammatory Bowel Disease Patients

The inflammatory bowel diseases (IBD), comprising mainly Crohn's disease (CD) and ulcerative colitis (UC), are characterized by chronic intestinal inflammation driven in part by complex genetic and gene regulatory mechanisms. Although transcriptomic studies have defined broad expression changes in IBD, the contribution of alternative splicing to disease-associated molecular variation remains less clear. We therefore integrated differential expression (DE) and differential splicing (DS) analyses in macroscopically uninvolved colonic mucosal biopsies from patients with either CD or UC along with non-IBD controls to define gene expression and intron-usage changes across disease subtypes. We identified 491 DS and 316 DE genes in CD vs. non-IBD, and 1,298 DS and 1,107 DE genes in UC vs. non-IBD. DS and DE genes were nearly mutually exclusive, with no overlapping genes in CD and 16 in UC. Consistent with this result, pathway analysis showed that differentially expressed and differentially spliced genes were associated with related but distinct biological programs. DE genes were involved in chromatin organization, transcriptional regulation, and metabolic pathways for glycans and drugs, whereas DS genes were enriched for splicing, cellular signaling, and lipid metabolism. We found substantial similarity in enriched pathways across CD and UC with some notable exceptions, including increased enrichment of DS and DE genes involved in extracellular vesicles and exosomes in CD and enrichment of DS genes in ER-to-Golgi trafficking and stress granules in UC. Direct comparisons of CD and UC patients additionally show differential splicing usage in genes involved in cell adhesion pathways. These findings identify alternative splicing as a major contributor to transcriptomic changes in IBD that is largely distinct from changes in expression level and provide a broader view of molecular contributors to IBD.

genomics↗

bioRxiv2026

Fatty Acid Oxidation Suppression Reprograms Fibroblasts in Fibrostenotic Crohns Disease

Fibrostenotic complications represent a major cause of morbidity in Crohns disease (CD), yet the cellular mechanisms that drive intestinal fibrosis independent of active inflammation remain poorly understood. Here, we identify impaired fatty acid oxidation (FAO) as a defining metabolic feature of fibroblasts in fibrostenotic CD. Untargeted lipidomics of non-inflamed colonic tissue from CD patients demonstrated enrichment of triacylglycerols and long-chain acylcarnitines, suggesting altered lipid utilization. Across three independent RNA-sequencing cohorts, including treatment-naive pediatric ileal biopsies, FAO genes (CPT1A, CPT2, SLC25A20) were selectively downregulated in patients with or destined to develop fibrostenotic disease. Single-cell RNA-sequencing localized these transcriptional alterations specifically to fibroblasts within strictured ileum. Primary fibroblasts derived from fibrostenotic CD exhibited increased neutral lipid accumulation, impaired mitochondrial fatty acid trafficking, and diminished responsiveness to PPAR{gamma}-mediated suppression of TGF{beta}-induced myofibroblast activation. Together, these findings demonstrate that FAO impairment is a conserved, fibroblast-specific metabolic program associated with intestinal fibrosis in CD and suggest that metabolic modulation of stromal cells represents a potential therapeutic strategy for fibrostenotic disease.

genomics↗

bioRxiv2025

Reference-guided Genome Assembly of Long Non-coding RNA Transcripts reveals Target Genes Associated With Crohn's Disease

Crohns disease (CD) is highly heterogeneous in presentation and progression with no cure. Molecular phenotyping has been used to elucidate cellular and tissue-based alterations to characterize drivers and effects of disease. One currently understudied class of functional molecules is long non-coding RNAs (lncRNAs). Studying the full lncRNA landscape in IBD is challenging due in part to an incomplete lncRNA annotation and a lack of their functional characterization in tissues of interest. We used a genome-guided alignment strategy to assemble predicted lncRNA transcripts using short RNA-sequencing data from colon tissue of adult patient samples. When combining our predicted lncRNAs with previous lncRNA annotations, we determined 98 that were differentially expressed, recapitulating many from previous IBD studies while also uncovering new ones. We built gene co-expression networks to cluster lncRNAs with functionally characterized protein-coding genes. Clusters containing differential lncRNAs were correlated to disease status and associated with pathways related to the humoral immune response, metabolism, and tissue regeneration. We uncovered multiple differential lncRNAs whose expression significantly correlated with nearby differential protein-coding genes that have also been differentially expressed in other IBD datasets, such as PITX2. We focused on a predicted lncRNA that is antisense to the PITX2-adjacent lncRNA PANCR, which we called PANCR-AS1, and provide multiple lines of evidence that support PANCR-AS1 functioning as an enhancer of PITX2 expression. Overall, we determined lncRNAs that are potential contributors to CD pathogenesis. We developed a robust pipeline for identifying lncRNAs in diseased and non-diseased tissue that are absent from reference annotations. We also outlined a framework to pinpoint significant disease-associated lncRNAs with potential functional activity related to their nearby protein-coding genes.

genomics↗