Journal: Frontiers in Genetics

Article Title: Deciphering the role of CNIH4 in pan-cancer landscapes and its significance in breast cancer progression

doi: 10.3389/fgene.2025.1536620

Figure Lengend Snippet: (A) Expression of CNIH4 gene in each microdomain in BRCA spatial transcriptome sections; (B–E) The cell type with the largest proportion in each microdomain at BRCA idle resolution and the spatial transcriptome localization of the CNIH4 gene. Each dot is a spot for spatial transcriptome sequencing, and different colors represent different cell types. The darker the color (red) in the same spot, the higher the expression of the CNIH4 gene in the spot; (F–I) Spearman correlation of CNIH4 gene expression with each cell type in microdomains at idle resolution. The red line indicates a positive correlation, the green line denotes a negative correlation, the gray line signifies no statistical significance, and the thickness of the line reflects the absolute value of the correlation coefficient.

Article Snippet: Spatial transcriptome datasets were obtained from the 10x Genomics server ( https://www.10xgenomics.com/ ) and previous studies ( ; ). provide details of the spatial transcriptome dataset and detailed abbreviations for the 33 tumors.

Techniques: Expressing, Sequencing, Gene Expression

Journal: Nucleic Acids Research

Article Title: SPathDB: a comprehensive database of spatial pathway activity atlas

doi: 10.1093/nar/gkae1041

Figure Lengend Snippet: Overview of data content and functions of SPathDB. The left panel contains the database content, which includes the spatial transcriptome dataset and pathway data content, and construction of spatial pathway activity profiles. The right panel contains the tools of SPathDB to retrieve, analyze and visualize spatial pathway activity.

Article Snippet: Spatial transcriptome datasets of human and mouse were collected from the Gene Expression Omnibus (GEO) database , 10× Genomics ( https://www.10xgenomics.com/ ), Mendeley Data ( https://data.mendeley.com/ ) and CROST ( https://ngdc.cncb.ac.cn/crost/ ).

Techniques: Activity Assay

Journal: Nature

Article Title: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ

doi: 10.1038/s41586-025-09803-4

Figure Lengend Snippet: (A, C) Total and (B, D) virus-specific ASCs were quantified in the liver at week 4 post-infection for (A, B) RHV and (C, D) LCMV clone 13 infection with (E, F) representative ELISpot images showing (A, B) representative and (C, D) pooled data from (A-D) n = 2 independent experiments. Mice were either untreated (WT) or splenectomized and treated with FTY720 prior to infection with treatment being maintained throughout (splX + FTY720 [D -1]). Virus localization was determined by viral transcript density for individual portal and central zones at week 1 post-infection during (G) RHV and (H) LCMV clone 13 infection from n = 10 portal and n = 10 central zone selections from a Xenium 5 K spatial transcriptomics run of n = 1 mouse liver per group. Transcript density of genes associated with oxidative phosphorylation usage were quantified in (I) portal zone hepatocyte regions and (J) immature lymphocytic clusters at week 1 post-infection. Following (K) upstream staining, (L-O) individual transcript localization was determined in the liver at week 1 post-infection. (A-D, G-J) Mean + SEM. (A-D, G-J) Two-tailed, unpaired t-tests were performed. (A) p = 0.9168, (B) p = 0.1987, (C) p = 0.0008, (D) p < 0.0001, (G) p = 0.0261, (H) p = 0.0282. Statistical significance was denoted as *=(p ≤ 0.05), **=(p ≤ 0.01), ***=(p ≤ 0.001), and ****=(p ≤ 0.0001).

Article Snippet: Fig. 5 Hepaciviral infection in mouse and human induce intrahepatic lymphoid structures with highly similar cellular composition, organizational microarchitecture and cell–cell contacts. a , b , Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining ( a ) and selected transcript localization ( b ). c – g , Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm of tissue ( c ), aggregate area of leukocytic aggregates ( d ), and lymphocytic cell-type proportions of B cells ( e ), CD4 + T cells ( f ) and CD8 + T cells ( g ) observed in leukocytic aggregates from individuals with AIH ( n = 1), chronic HBV ( n = 2) and chronic HCV ( n = 2) infection.

Techniques: Virus, Infection, Enzyme-linked Immunospot, Phospho-proteomics, Staining, Two Tailed Test

Journal: Nature

Article Title: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ

doi: 10.1038/s41586-025-09803-4

Figure Lengend Snippet: a – c , H&E staining of formalin-fixed, paraffin-embedded (FFPE) spleen ( a ) and mesenteric lymph node ( b ) sections at 4 weeks post-LCMV infection and a liver section at 4 weeks post-RHV infection ( c ). Regions of interest (ROIs) are enlarged on the right. One tissue sample from each condition was utilized for Visium HD spatial transcriptomics based on similar morphological H&E staining with limited interindividual variability for n = 4 ( a ), n = 4 ( b ) and n = 5 ( c ) mice. d – h , Visium HD spatial transcriptomic of slides shown in a – c . Individual transcript localization is shown as log 2 -scaled heat maps of 8-μm bins for Ms4a1 ( d ), H2afx ( e ), Cd3g ( f ), Ccl21a ( g ) and Xbp1 ( h ). i , Graph-based subclustering of clusters of interest from sections in a – c were manually annotated and cross-validated with ACT and PanglaoDB cell annotation databases. IFZ, interfollicular zone; SCS, subcapsular sinus. Colours indicate cell type and anatomical zones.

Article Snippet: Fig. 5 Hepaciviral infection in mouse and human induce intrahepatic lymphoid structures with highly similar cellular composition, organizational microarchitecture and cell–cell contacts. a , b , Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining ( a ) and selected transcript localization ( b ). c – g , Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm of tissue ( c ), aggregate area of leukocytic aggregates ( d ), and lymphocytic cell-type proportions of B cells ( e ), CD4 + T cells ( f ) and CD8 + T cells ( g ) observed in leukocytic aggregates from individuals with AIH ( n = 1), chronic HBV ( n = 2) and chronic HCV ( n = 2) infection.

Techniques: Staining, Formalin-fixed Paraffin-Embedded, Infection

Journal: Nature

Article Title: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ

doi: 10.1038/s41586-025-09803-4

Figure Lengend Snippet: (A-F) Visium HD spatial transcriptomic outputs at 4 weeks post-RHV infection in the liver displayed as log2-scaled heatmaps of 8 μm bins for single-parameter panels and feature sums for multiple-parameter lists. (A) Transcripts characteristic of central zone (zone 3) are shown in orange ( Glul, Cyp2e1 ) while those characteristic of portal zone (zone 1) are shown in green ( Hal, Arg1 ). (B) Co-expression of central (orange) and portal (green) zone-related transcripts shown in (A) as combined feature sums. (C) Merged expression of central (red, Glul and Cyp2e1 ) and portal (green, Hal and Arg1 ) combined transcripts. (D) Expression of various plasma cell-related transcripts as shown in blue ( Xbp1 , Derlr3 , Jchain , Irf4 ). (E) Merged expression of transcripts indicative of the central zone (red, Glul and Cyp2e1 ) and plasma cells ( Xbp1 , Derl3 , Jchain , Irf4 ). (F) Merged expression of transcripts indicative of the portal zone (green, Hal and Arg1 ) and plasma cells ( Xbp1 , Derl3 , Jchain , Irf4 ). (F) Co-expression of plasma cell-related transcripts ( Xbp1 , Derl3 , Jchain , Irf4 ) as feature sum list. (A, F) From morphologically similar H&E staining with limited interindividual variability conducted on n = 5 mice, data is shown from n = 1 mouse liver tissue with which Visium HD spatial transcriptomics was conducted.

Article Snippet: Fig. 5 Hepaciviral infection in mouse and human induce intrahepatic lymphoid structures with highly similar cellular composition, organizational microarchitecture and cell–cell contacts. a , b , Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining ( a ) and selected transcript localization ( b ). c – g , Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm of tissue ( c ), aggregate area of leukocytic aggregates ( d ), and lymphocytic cell-type proportions of B cells ( e ), CD4 + T cells ( f ) and CD8 + T cells ( g ) observed in leukocytic aggregates from individuals with AIH ( n = 1), chronic HBV ( n = 2) and chronic HCV ( n = 2) infection.

Techniques: Infection, Expressing, Clinical Proteomics, Staining

Journal: Nature

Article Title: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ

doi: 10.1038/s41586-025-09803-4

Figure Lengend Snippet: a – c , Visium HD spatial transcriptomics from liver tissue at four weeks post-RHV infection. a , Transcript feature sums of log 2 -scaled heat maps of 8-μm bins for osteopontin ( Spp1 ), Cxcl12 , type I collagen ( Col1a1 and Col1a2 ( Col1a1/2 )), Icam2 , fibronectin ( Fn1 ), Cd44 , Cxcr4 , CD138 ( Sdc1 ), LFA-1 ( Itga4 / Itgb1 ) and VLA-4 ( Itgal/Itgb7 ). b , Merged transcript localization of feature sum lists from a . c , H&E image with portal vein (blue) and central vein (yellow) ROIs (left) with associated transcript localization (right). d , Cartoon diagram representing plausible molecular factors responsible for intrahepatic plasma cell retention. LSEC, liver sinusoidal endothelial cell. Created in BioRender. Grakoui, A. (2025) https://BioRender.com/ppmu1j5 . e , f , Intrahepatic total ( e ) and E2-specific ( f ) ASCs at 4 weeks post-infection with or without acute blockade of anchoring molecules at days 26 and 27 post-infection. AMD, AMD3100; anti-V/L, anti-VLA-4 plus anti-LFA-1; anti-V/L/S, anti-VLA-4, anti-LFA-1 plus anti-SPP1. n = 2 independent experiments. Control versus anti-V/L + AMD: P = 0.0003 ( e ), P = 0.0182 ( f ). g – i , Xenium Prime 5K spatial transcriptomics on liver tissue at three weeks post-infection with upstream morphological staining ( g ), virus, vasculature and plasma cell transcript localization ( h ), and virus, GC-associated and plasma cell transcript localization in periportal regions ( i ). j , RHV RNA in serum plotted against intrahepatic E2-specific ASC frequencies at four weeks post-infection. μMT, B6.129S2-Ighmtm1Cgn/J mice lacking mature B cells; dpi, days post infection. k , l , Bulk IgH BCR sequencing at 4 weeks post-infection from n = 3 RHV-infected mice, n = 3 LCMV-infected mice and n = 1 naive mouse. SHM accrual is plotted as nucleotide divergence from germline sequences among distinct clonotypes ( k ) and IgH V–J gene pairing chord diagrams ( l ). m – o , Intrahepatic common Igkc transcript localization alongside unique Igkv gene family transcripts with upstream morphological staining ( m ) and segmented cell borders showing transcript localization of Igkc with Igkv4-51 ( n ) and Igkc with Igkv15-103 ( o ). e , f , j , Data are representative or pooled values from at least two independent experiments of at least three mice per group. e , f , k , Data are mean + s.e.m. One-way ANOVA with Tukey’s multiple comparisons test ( e , f , k ); two-tailed nonparametric Spearman correlations with Pearson’s r ( j ).

Article Snippet: Fig. 5 Hepaciviral infection in mouse and human induce intrahepatic lymphoid structures with highly similar cellular composition, organizational microarchitecture and cell–cell contacts. a , b , Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining ( a ) and selected transcript localization ( b ). c – g , Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm of tissue ( c ), aggregate area of leukocytic aggregates ( d ), and lymphocytic cell-type proportions of B cells ( e ), CD4 + T cells ( f ) and CD8 + T cells ( g ) observed in leukocytic aggregates from individuals with AIH ( n = 1), chronic HBV ( n = 2) and chronic HCV ( n = 2) infection.

Techniques: Infection, Clinical Proteomics, Control, Staining, Virus, Sequencing, Two Tailed Test

Journal: Nature

Article Title: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ

doi: 10.1038/s41586-025-09803-4

Figure Lengend Snippet: (A) Number of total IgG + ASCs in the liver at week 4 post-RHV infection following splenectomy one week prior to infection or FTY720 administration beginning at day 11 post-infection onward with representative ELISpot image. (B) Correlation between % plasma cells (CD38 low CD138 + of total B cells) and % GC B cells (CD38 low CD95 + of total B cells) in the liver at 4 weeks post-infection with RHV. (C) Representative H&E staining of FFPE sections from spleen at week 4 post-LCMV infection and liver at week 4 post-RHV infection. (D) Immunofluorescence staining of FFPE sections at 4 weeks post-RHV infection. Localization of representative Ig kappa gene families displayed as log2-scaled heatmaps of 8 μm bins at 4 weeks post-infection in (E) spleen (LCMV), (F) mesenteric lymph nodes (LCMV) and (G) liver (RHV). (H) From liver tissue at 4 weeks post-infection with RHV following FTY720 treatment, H&E (top) is shown for corresponding ROIs where Igkv19–93 localization is shown as log2-scaled heatmaps of 8 μm bins (bottom). (I) Correlation between intrahepatic CD38 low CD95 + GC B cells and RHV serum viremia at 4 weeks post-infection. (A-B) Data shown are representative or pooled values from 2-3 independent experiments of 3–9 mice per group. Visium HD spatial transcriptomics was conducted with liver tissue from n = 1 representative mouse following similar H&E morphological staining with limited interindividual variability from (C) n = 4 (spleen) and n = 4 (liver), (E) n = 4, (F) n = 4, (G) n = 5, and (H) n = 4 mice. (D) Representative image shown from immunofluorescent staining that was performed with liver tissue from n = 4 mice. (A) Mean + SEM. Statistical tests performed were (A) one-way ANOVA with Tukey’s multiple comparisons test and (B, I) two-tailed nonparametric Spearman correlation with Pearson’s r coefficient. (A) Uninfected vs. WT: p < 0.0001, WT vs. FTY720 D + 11: p = 0.9939, FTY720 D + 11 vs. Splenectomy: p = 0.9853. Statistical significance was denoted as ****=(p ≤ 0.0001).

Article Snippet: Fig. 5 Hepaciviral infection in mouse and human induce intrahepatic lymphoid structures with highly similar cellular composition, organizational microarchitecture and cell–cell contacts. a , b , Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining ( a ) and selected transcript localization ( b ). c – g , Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm of tissue ( c ), aggregate area of leukocytic aggregates ( d ), and lymphocytic cell-type proportions of B cells ( e ), CD4 + T cells ( f ) and CD8 + T cells ( g ) observed in leukocytic aggregates from individuals with AIH ( n = 1), chronic HBV ( n = 2) and chronic HCV ( n = 2) infection.

Techniques: Infection, Enzyme-linked Immunospot, Clinical Proteomics, Staining, Immunofluorescence, Two Tailed Test

Journal: Nature

Article Title: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ

doi: 10.1038/s41586-025-09803-4

Figure Lengend Snippet: a , b , Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining ( a ) and selected transcript localization ( b ). c – g , Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm 2 of tissue ( c ), aggregate area of leukocytic aggregates ( d ), and lymphocytic cell-type proportions of B cells ( e ), CD4 + T cells ( f ) and CD8 + T cells ( g ) observed in leukocytic aggregates from individuals with AIH ( n = 1), chronic HBV ( n = 2) and chronic HCV ( n = 2) infection. Data are mean + s.e.m. d – g , One-way ANOVA with Tukey’s multiple comparisons test. AIH versus HBV: P = 0.0101 ( g ). h , Quantification of cell types and their direct contact partners within leukocytic aggregates from annotated spatial transcriptomics with subcellular resolution and cell segmentation during mouse RHV (orange) and human HCV (blue) infection. HSC, hepatic stellate cell. i – n , RHV-infected mouse liver ( i , k , m ) and HCV-infected human liver ( j , l , n ) tissue. Generative GC-like structures were characterized upstream staining ( i , j ) and GC-associated transcript localization ( k , l ) and colour-coded cell-type annotation with selected overlaid transcripts ( m , n ). o – t , RHV-infected mouse liver ( o , q , s ) and HCV-infected human liver ( p , r , t ) tissue. Areas of intrahepatic plasma cell residency were characterized by upstream staining ( o , p ) and plasma cell and hepatic stellate cell and fibroblast-associated transcripts ( q , r ) with colour-coded cell-type annotation ( s , t ). Based on similar morphological H&E staining with limited interindividual variability of n = 2 HCV-infected humans and n = 4 RHV-infected mice, Xenium 5K was performed on tissue from n = 2 human and n = 1 mouse livers, from which n = 1 representative tissue of each are shown in i – t .

Article Snippet: Fig. 5 Hepaciviral infection in mouse and human induce intrahepatic lymphoid structures with highly similar cellular composition, organizational microarchitecture and cell–cell contacts. a , b , Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining ( a ) and selected transcript localization ( b ). c – g , Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm of tissue ( c ), aggregate area of leukocytic aggregates ( d ), and lymphocytic cell-type proportions of B cells ( e ), CD4 + T cells ( f ) and CD8 + T cells ( g ) observed in leukocytic aggregates from individuals with AIH ( n = 1), chronic HBV ( n = 2) and chronic HCV ( n = 2) infection.

Techniques: Infection, Staining, Clinical Proteomics

Journal: Nature

Article Title: iHALT unlocks liver functionality as a surrogate secondary lymphoid organ

doi: 10.1038/s41586-025-09803-4

Figure Lengend Snippet: Xenium Prime 5 K spatial transcriptomics was performed with liver tissue obtained during human (A, B) AIH and (C, D) HBV infection. Depicted are regions of interest showing (A, C) upstream morphological staining and (B, D) expression of various color-coded transcripts and annotated cell types. Data shown from (A, B) n = 1 individual with AIH and (C, D) n = 1 individual chronically infected with HBV from which liver tissue was selected for spatial transcriptomics conducted on (A, B) n = 1 individual and (C, D) n = 2 individuals with limited interindividual variability.

Article Snippet: Fig. 5 Hepaciviral infection in mouse and human induce intrahepatic lymphoid structures with highly similar cellular composition, organizational microarchitecture and cell–cell contacts. a , b , Xenium Prime 5K spatial transcriptomics of liver tissue from healthy, AIH, HBV-infected and HCV-infected humans with upstream staining ( a ) and selected transcript localization ( b ). c – g , Quantitative analyses from spatial transcriptomics demonstrating number of leukocytic aggregates per mm of tissue ( c ), aggregate area of leukocytic aggregates ( d ), and lymphocytic cell-type proportions of B cells ( e ), CD4 + T cells ( f ) and CD8 + T cells ( g ) observed in leukocytic aggregates from individuals with AIH ( n = 1), chronic HBV ( n = 2) and chronic HCV ( n = 2) infection.

Techniques: Infection, Staining, Expressing

Journal: Computational and Structural Biotechnology Journal

Article Title: Spatial domains identification in spatial transcriptomics using modality-aware and subspace-enhanced graph contrastive learning

doi: 10.1016/j.csbj.2024.10.029

Figure Lengend Snippet: GRAS4T improved the accuracy of identifying layer structures within the DLPFC dataset compared to other methods. (a) Boxplot of ARI values across all sections of the DLPFC dataset for six methods. (b) The H&E image and manual annotation of slice 151672. (c) The spatial domains in six methods for slice 151672. (d) UMAP visualizations and PAGA graphs in six methods for slice 151672.

Article Snippet: The ST datasets supporting the findings of this study are all publicly available. (1) The DLPFC dataset is available at http://research.libd.org/spatialLIBD/ . (2) The HER2+ dataset generated by spatial transcriptomics platform is accessed at https://github.com/almaan/her2st . (3) The mouse visual cortex dataset generated by STARmap is available at https://www.dropbox.com/sh/f7ebheru1lbz91s/AADm6D54GSEFXB1feRy6OSASa/visual_1020/20180505_BY3_1kgenes?dl=0&subfolder_nav_tracking=1 . (4) The adult mouse brain dataset is accessed at https://www.10xgenomics.com/resources/datasets . (5) The Stereo-seq mouse olfactory bulb dataset is available at https://github.com/JinmiaoChenLab/SEDR_analyses/ . (6) The MERFISH dataset is accessed at https://datadryad.org/stash/dataset/doi:10.5061/dryad.8t8s248 . (7) The human breast cancer dataset is available at https://www.10xgenomics.com/resources/datasets . (8) The anterior and posterior sections of the mouse brain are accessed at https://www.10xgenomics.com/resources/datasets and the Allen Brain Atlas reference is available at https://mouse.brain-map.org/static/atlas .

Techniques: