Journal: European Journal of Medical Research

Article Title: Total fat intake and fatty acid patterns and prediabetes regression: differential effects across phenotypes in a population-based cohort

doi: 10.1186/s40001-025-02337-5

Figure Lengend Snippet: Heatmap of the correlations between the dietary fatty acids and fat patterns with overall mean of FSG and 2 h-SG overtime across Pre-DM phenotypes. The color represents the intensity of the Spearman correlation coefficients. * Indicates P < 0.05

Article Snippet: Correlations (and P values) between logarithm (Log 10 ) of fatty acids and PCA-derived fat patterns score with overall mean of FSG and 2 h-SG overtime across Pre-DM phenotypes were performed using Pearson correlation coefficients, and correlation plots were visualized using the STATA heatmap function.

Techniques:

Journal: Nature immunology

Article Title: Bcl-6 is the nexus transcription factor of T follicular helper cells (T FH ) via repressor-of-repressor circuits

doi: 10.1038/s41590-020-0706-5

Figure Lengend Snippet: a , A hypothetical model of Bcl-6 on the regulation of non-T FH and T FH genes. Bcl6-r, genes repressed by Bcl-6. Bcl6-rr, genes repressed by repressors that are repressed by Bcl-6. b , Schematic of the SMARTA cell transfer system used for RNA-seq analysis. T H 1 (CXCR5 lo SLAM hi ) populations from wild-type and Bcl6 f/f Cre CD4 SMARTA cells, T FH (CXCR5 hi SLAM lo ) populations from wild-type and Prdm1 f/f Cre CD4 SMARTA cells, T H 1-like (CXCR5 lo SLAM int ) and T FH -like (CXCR5 + SLAM int ) populations from Bcl6 f/f Prdm1 f/f Cre CD4 SMARTA cells were sorted from spleens of C57BL/6 host mice given wild-type, Bcl6 f/f , Prdm1 f/f , and Bcl6 f/f Prdm1 f/f Cre CD4 SMARTA CD4 + T cells, followed by infection of the host mice with LCMV Arm , and analyzed 7 days later. Naive SMARTA cells were isolated as CD44 lo CD62L hi CD45.1 + from uninfected mice. Representative flow cytometry of T FH , T H 1, T FH -like, and T H 1-like subsets from three independent experiments. c , Upper, scatter plot of genes upregulated (red) or downregulated (blue) in T FH cells relative to their expression in T H 1 cells (1.4-fold cut off, Adj. P <0.05). Lower, volcano plots of gene expression changes between wild-type T FH cells and Bcl6 f/f Prdm1 f/f T FH -like cells (horizontal axis) against Adj. P -value (vertical axis). Numbers indicate total and percent of those genes upregulated in wild-type T FH cells (top left) or Bcl6 f/f Prdm1 f/f T FH -like cells (top right). T H 1 cell-associated genes, upregulated in wild-type T H 1 cells versus wild-type T FH cells (WT T H 1 > WT T FH ); T FH cell-associated genes, upregulated in wild-type T FH cells versus wild-type T H 1 cells (WT T FH > WT T H 1). Adj. P -values for multiple test correction were determined using Benjamini-Hochberg algorithm. d , Gene expression changes were clustered by MAP-DP analysis. Scale, row z-score. DKO, Bcl6 f/f Prdm1 f/f Cre CD4 . e , Left, a hypothetical model of Bcl-6 regulation of Bcl6-rr T FH + genes in Cluster 4 by inhibition of Bcl6-r TFs in Cluster 1. Right, a hypothetical model of Blimp-1 regulation of Blimp-1-rr T H 1 + genes in Cluster 2 by inhibition of Blimp-1-r TFs in Cluster 3. f , Multiple gene set enrichment analyses (GSEA) for identifying and comparing gene signatures in CD4 + T cells between subpopulations. Blue indicates a negative association, and red indicates a positive association. Circle size is proportional to NES (scale: 1.5–3.0). Tint indicates adjusted P -value that were corrected using Benjamini-Hochberg algorithm. g , GSEA of BCL-6 bound genes from human tonsillar GC-T FH compared to Cluster 1 genes (left) or Cluster 4 genes (right) differentially expressed between Bcl6 f/f Prdm1 f/f T FH -like cells and Prdm1 f/f T FH cells. The ticks below the line correspond to the rank of each gene that is defined by p-value of gene expression change between Bcl6 f/f Prdm1 f/f T FH -like and Prdm1 f/f T FH . NES, normalized enrichment score; FDR, false discovery rate. h , GSEA of Blimp-1 bound genes from activated CD8 T cells in comparison of Cluster 3 genes differentially expressed between Bcl6 f/f Prdm1 f/f T H 1-like cells and Bcl6 f/f T H 1 cells.

Article Snippet: P -val <0.05) using hclust function from stats package in R and the heatmap was generated using heatmap.2 function from gplots package in R. Gene Set Enrichment Analysis (GSEA) was run on gene lists pre-ranked by DESeq log P -value multiplied by the sign of the log-fold change with GSEA v3.0 (Broad Institute, Inc.).

Techniques: RNA Sequencing, Infection, Isolation, Flow Cytometry, Expressing, Gene Expression, Inhibition, Comparison

Journal: Nature immunology

Article Title: Bcl-6 is the nexus transcription factor of T follicular helper cells (T FH ) via repressor-of-repressor circuits

doi: 10.1038/s41590-020-0706-5

Figure Lengend Snippet: Related to a , Schematic of the SMARTA cell transfer system used for RNA-seq analysis in KLH-gp 61 immunization. Non-T FH (CXCR5 lo PSGL1 hi ) populations from WT, Bcl6 f/f Cre Cd4 , Prdm1 f/f Cre CD4 , or Bcl6 f/f Prdm1 f/f Cre Cd4 SMARTA cells and T FH (CXCR5 hi PSGL1 lo ) populations from WT or Prdm1 f/f Cre CD4 SMARTA cells were sorted from C57BL/6 host mice given WT, Bcl6 f/f , Prdm1 f/f , or Bcl6 f/f Prdm1 f/f Cre CD4 SMARTA CD4 T cells, followed by infection of the host mice with KLH-gp 61 in alum + cGAMP, and analyzed 8 days later. Naive SMARTA cells were isolated as CD44 lo CD62L hi CD45.1 + from uninfected mice. Representative flow cytometry of T FH and T H 1 subsets from four independent experiments. b , Heatmap of gene expression of curated T FH -associated genes. Scale, row z-score. DKO, Bcl6 f/f Prdm1 f/f Cre CD4 . As a first analysis the effect of Bcl6 / Prdm1 double-deficiency on the T FH biology, we assessed expression of a broad curated set of T FH -associated genes across all samples from RNA-seq gene expression profiling. Bcl6 f/f Prdm1 f/f Cre CD4 T FH -like cells lost expression of positively T FH -associated genes in comparison to WT T FH cells or Prdm1 f/f Cre CD4 T FH cells. Conversely, Bcl6 f/f Prdm1 f/f Cre CD4 T H 1-like cells had a gene expression profile different from WT T H 1 or Bcl6 f/f Cre CD4 T H 1 cells. c , Principal component analysis of differential gene expression from RNA-seq of LCMV Arm infection. Principal component analysis provided similar findings as (b), supporting the overall hypothesis that T FH is not a default differentiation pathway of CD4 + T cells and Bcl-6 has important activities beyond inhibition of Prdm1 . d , Gene expression changes were clustered by K-means clustering analysis (K=10) of LCMV Arm infection. e , Hierarchical clustering analysis of genes upregulated or downregulated in T FH cells relative to their expression in T H 1 cells (1.4-fold cut off, Adj. P <0.05) of LCMV Arm infection shown in . Scale, row z-score. f , GSEA of BCL-6 bound genes from human tonsillar GC-T FH compared to Cluster 2 genes (left) or Cluster 3 genes (right) differentially expressed between Bcl6 f/f Prdm1 f/f T FH -like cells and Prdm1 f/f T FH cells. NES, normalized enrichment score; FDR, false discovery rate. g , GSEA of Blimp-1 bound genes from CD8 and T H 17 cells in comparison of Cluster 2 and Cluster 3 genes differentially expressed between Bcl6 f/f Prdm1 f/f T H 1-like cells and Bcl6 f/f T H 1 cells.

Article Snippet: P -val <0.05) using hclust function from stats package in R and the heatmap was generated using heatmap.2 function from gplots package in R. Gene Set Enrichment Analysis (GSEA) was run on gene lists pre-ranked by DESeq log P -value multiplied by the sign of the log-fold change with GSEA v3.0 (Broad Institute, Inc.).

Techniques: RNA Sequencing, Infection, Isolation, Flow Cytometry, Gene Expression, Expressing, Comparison, Inhibition

Journal: Nature immunology

Article Title: Bcl-6 is the nexus transcription factor of T follicular helper cells (T FH ) via repressor-of-repressor circuits

doi: 10.1038/s41590-020-0706-5

Figure Lengend Snippet: a , Gene expression of Id2 from RNA-seq data of LCMV Arm infected mice or KLH-gp 61 immunized mice. Each data point was collected from three (LCMV Arm ) or four (KLH-gp 61 ) independent experiments. b , GSEA of E2A bound genes from thymocytes , in comparison to Cluster 4 genes between Bcl6 f/f Prdm1 f/f T FH -like cells and Prdm1 f/f T FH cells. c , A hypothetical model of Bcl-6 regulation of T FH genes primarily via inhibition of Id2 and Prdm1 /Blimp-1. d , Schematic of the SMARTA cell transfer system used for KLH-gp 61 immunization. Wild-type, Bcl6 f/f Prdm1 f/f , or Bcl6 f/f Prdm1 f/f Id2 f/f Cre CD4 SMARTA CD4 + T were transferred to C57BL/6 host mice, followed by immunization of the host mice with KLH-gp 61 in alum + cGAMP, and analyzed 8 days later. See Fig. 4e,f and . e,f , Representative flow cytometry of CXCR5 hi T FH , CXCR5 hi PD-1 hi and CXCR5 hi PSGL1 lo GC-T FH SMARTA cell subsets from dLNs of KLH-gp 61 immunized mice in Fig.4d. Two independent experiments were performed; each dot represents one mouse (n = 4). Data are mean ± s.d., unpaired two-tailed Student’s t-test. , Quantification of CXCR5 hi SLAM lo T FH and CXCR5 hi PSGL1 lo GC-T FH cells, gated on SMARTA cells from spleens of LCMV Arm infected mice. Two independent experiments were performed; each dot represents one mouse (n = 4). Data are mean ± s.d., unpaired two-tailed Student’s t-test. See – .

Article Snippet: P -val <0.05) using hclust function from stats package in R and the heatmap was generated using heatmap.2 function from gplots package in R. Gene Set Enrichment Analysis (GSEA) was run on gene lists pre-ranked by DESeq log P -value multiplied by the sign of the log-fold change with GSEA v3.0 (Broad Institute, Inc.).

Techniques: Gene Expression, RNA Sequencing, Infection, Comparison, Inhibition, Flow Cytometry, Two Tailed Test