Journal: iScience

Article Title: Calcineurin/NFATc2 and PI3K/AKT signaling maintains β-cell identity and function during metabolic and inflammatory stress

doi: 10.1016/j.isci.2022.104125

Figure Lengend Snippet: Identification of genes and transcription factors that regulate β-cell differentiation and disallowed genes in human islets exposed to metabolic and inflammatory stress (A) Relative abundance of RNA-Seq differentially expressed mRNA transcripts determined by DESeq2 average normalized count values for β-cell differentiation and disallowed genes in human islets exposed to 16.7 mM glucose (G16.7) and IL-1β. (B and C) Enrichr enrichment analysis visualization grid, network, and bar graph and (C) table of results ranked by combined score of odds ratio and p value (p < 0.05) as determined by TRANSFAC and JASPAR software analyses of position weight matrices of transcription factors for gene targets identified by RNA-Seq (padj <0.05). The grid represents enriched terms that cluster with highest significance. Network nodes represent enriched terms and links represent gene content similarity among enriched terms. Brighter colors represent higher significance.

Article Snippet: Figure 2 Requirements of CN and NFATc2 to regulate genes controlling β-cell identity and function (A) Scatterplot of gene sets clustered by relatedness to integrated pathways affected by FK506 inhibition of CN in human islets exposed to 16.7 mM glucose (G16.7) and IL-1β. (B) Volcano plot of p values of associated integrated pathway gene sets with corresponding odds ratio. (C) Top integrated pathways affected by FK506 in human islets determined by cumulative p value and odds ratio as shown in the table. (A-C) Darker blue shading represents decreasing p value and gray points are not significant (p > 0.05) where lighter shades represent increasing p values as determined by Enrichr software analyses of position weight matrices of transcription factors for gene targets identified by RNA-Seq. (Enrichr/NIH BioPlanet, padj <0.01). (D) Top β-cell development and functional genes affected by FK506 in human islets (Enrichr/NIH BioPlanet, padj <0.05). (E) Heatmap comparing effects of 16.7mM glucose and cytokines, CN inhibitor FK506, or NFATc2βKO on fold change expression of β-cell differentiation genes and disallowed genes in human and mouse islets. (F) Venn diagram representing overlapping CN-dependent and NFATc2-dependent effects on upregulation (red arrows) and downregulation (blue arrows) of β-cell differentiation and disallowed genes in human islets and NFATc2βKO mouse islets, respectively (padj <0.05).

Techniques: Cell Differentiation, RNA Sequencing, Software

Journal: iScience

Article Title: Calcineurin/NFATc2 and PI3K/AKT signaling maintains β-cell identity and function during metabolic and inflammatory stress

doi: 10.1016/j.isci.2022.104125

Figure Lengend Snippet: Requirements of CN and NFATc2 to regulate genes controlling β-cell identity and function (A) Scatterplot of gene sets clustered by relatedness to integrated pathways affected by FK506 inhibition of CN in human islets exposed to 16.7 mM glucose (G16.7) and IL-1β. (B) Volcano plot of p values of associated integrated pathway gene sets with corresponding odds ratio. (C) Top integrated pathways affected by FK506 in human islets determined by cumulative p value and odds ratio as shown in the table. (A-C) Darker blue shading represents decreasing p value and gray points are not significant (p > 0.05) where lighter shades represent increasing p values as determined by Enrichr software analyses of position weight matrices of transcription factors for gene targets identified by RNA-Seq. (Enrichr/NIH BioPlanet, padj <0.01). (D) Top β-cell development and functional genes affected by FK506 in human islets (Enrichr/NIH BioPlanet, padj <0.05). (E) Heatmap comparing effects of 16.7mM glucose and cytokines, CN inhibitor FK506, or NFATc2βKO on fold change expression of β-cell differentiation genes and disallowed genes in human and mouse islets. (F) Venn diagram representing overlapping CN-dependent and NFATc2-dependent effects on upregulation (red arrows) and downregulation (blue arrows) of β-cell differentiation and disallowed genes in human islets and NFATc2βKO mouse islets, respectively (padj <0.05).

Article Snippet: Figure 2 Requirements of CN and NFATc2 to regulate genes controlling β-cell identity and function (A) Scatterplot of gene sets clustered by relatedness to integrated pathways affected by FK506 inhibition of CN in human islets exposed to 16.7 mM glucose (G16.7) and IL-1β. (B) Volcano plot of p values of associated integrated pathway gene sets with corresponding odds ratio. (C) Top integrated pathways affected by FK506 in human islets determined by cumulative p value and odds ratio as shown in the table. (A-C) Darker blue shading represents decreasing p value and gray points are not significant (p > 0.05) where lighter shades represent increasing p values as determined by Enrichr software analyses of position weight matrices of transcription factors for gene targets identified by RNA-Seq. (Enrichr/NIH BioPlanet, padj <0.01). (D) Top β-cell development and functional genes affected by FK506 in human islets (Enrichr/NIH BioPlanet, padj <0.05). (E) Heatmap comparing effects of 16.7mM glucose and cytokines, CN inhibitor FK506, or NFATc2βKO on fold change expression of β-cell differentiation genes and disallowed genes in human and mouse islets. (F) Venn diagram representing overlapping CN-dependent and NFATc2-dependent effects on upregulation (red arrows) and downregulation (blue arrows) of β-cell differentiation and disallowed genes in human islets and NFATc2βKO mouse islets, respectively (padj <0.05).

Techniques: Inhibition, Software, RNA Sequencing, Functional Assay, Expressing, Cell Differentiation