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Decreased GLUT2 expression and defective glucose uptake in MODY3 human iPSC-derived beta cells

ABSTRACT: To evaluate the impact of HNF1A+/H126D mutation on pancreatic beta cell biology, we performed RNA-Seq analyses on the day 20 endocrine progenitor cells which maximally expressed HNF1A. Principal component analysis (PCA) plot showed distinct clustering of WT cells separate from the mutant cells, indicating that the HNF1A+/H126D mutation has an impact on global transcript profiles in the cells. A volcano plot demonstrated that there were 1724 genes downregulated and only 583 genes upregulated in mutant cells as compared to WT cells. Gene ontology (GO) analysis revealed that the genes that were downregulated in mutant cells were largely involved in biological processes such as localization, transport and secretion and molecular functions such as protein binding and transporter activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140208 | GEO | 2021/03/22

REPOSITORIES: GEO

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Project description:Purpose: To elucidate the potential immune-regulatory mechanism of TRAIL of activated T cells in EAE, we analyzed gene expression profiles of splenic CD4+ T cells from EAE mice treated with TRAIL by RNA sequencing and transcriptome analysis. Methods: Splenic CD4+ T cell mRNA profiles of control or EAE mice treated with vehicle or TRAIL were generated by deep sequencing using Illumina Solexa. Library construction of all samples were used by Agilent's SureSelect Strand Specific RNA Library Preparation Kit for 75SE (Single-End or Paired-End) sequencing on Solexa platform. The sequence was directly determined using sequencing-by-synthesis technology via the TruSeq SBS Kit. Raw sequences were obtained from the Illumina Pipeline software bcl2fastq v2.0 and expected to generate 20M (million reads or Gb) per sample. Results: By comparing mRNA exression of splenic CD4+ T cells from EAE mice treated with vehicle or TRAIL, there were 244 genes significantly differentially expressed. By analyzing these 244 significant genes categorized by a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the most significantly enriched category for CD4+ T cells was “cell cycle” (multiple of enrichment: 3.13, p = 1.64 × 10−5) followed by “TCR signaling pathway” (multiple of enrichment: 2.80, p = 8.25 × 10−4). In addition, significant genes in the“TCR signaling pathway” tended to be downregulated while those in “cell cycle”tended to be upregulated in a volcano plot analysis. Consistent with the volcano plot results, by using unsupervised hierarchical clustering, the heatmap showed that significant TCR signaling pathway-associated genes were downregulated, while significant cell cycle-associated genes were upregulated in splenic CD4+ T cells from EAE mice treated with TRAIL Conclusions: Our study demonstrated the gene transcription pattern from CD4+ T cells of TRAIL-treated EAE mice were involved in distinct TCR signaling and cell cycle pathways.

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Decreased GLUT2 expression and defective glucose uptake in MODY3 human iPSC-derived beta cells

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