Distinct tumor-TAM interactions in IDH-stratified glioma microenvironments unveiled by single-cell and spatial transcriptomics DOI Creative Commons
Meysam Motevasseli, Maryam Darvishi, Alireza Khoshnevisan

et al.

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: Aug. 16, 2024

Tumor-associated macrophages (TAMs) residing in the tumor microenvironment (TME) are characterized by their pivotal roles progression, antitumor immunity, and TME remodeling. However, a thorough comparative characterization of tumor-TAM crosstalk across IDH-defined categories glioma remains elusive, likely contributing to mixed outcomes clinical trials. We delineated phenotypic heterogeneity TAMs IDH-stratified gliomas. Notably, two TAM subsets with mesenchymal phenotype were enriched IDH-WT glioblastoma (GBM) correlated poorer patient survival reduced response anti-PD-1 immune checkpoint inhibitor (ICI). proposed SLAMF9 receptor as potential therapeutic target. Inference gene regulatory networks identified PPARG, ELK1, MXI1 master transcription factors BMD-TAMs. Our analyses reciprocal interactions revealed distinct tumors, including ANXA1-FPR1/3, FN1-ITGAVB1, VEGFA-NRP1, TNFSF12-TNFRSF12A known contribution immunosuppression, proliferation, invasion recruitment. Spatially resolved transcriptomics further elucidated architectural organization highlighted communications. Furthermore, we demonstrated significant upregulation ANXA1, FN1, NRP1, TNFRSF12A genes tumors using bulk RNA-seq RT-qPCR. Longitudinal expression analysis candidate no difference between primary recurrent indicating that interactive network malignant states does not drastically change upon recurrence. Collectively, our study offers insights into unique cellular composition communication TME, revealing novel vulnerabilities for interventions GBM.

Language: Английский

Early brain gene network alterations and growth disruptions in juvenile Chinese longsnout catfish (Leiocassis longirostris) induced by 17β-estradiol and 17α-methyltestosterone DOI Creative Commons
Yang Feng, Hua Ye, Yong‐Qiang Deng

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2025, Volume and Issue: 293, P. 118053 - 118053

Published: March 1, 2025

Language: Английский

Citations

0
FOXM1 expression reverts aging chromatin profiles through repression of the senescence-associated pioneer factor AP-1 DOI Creative Commons
Fábio J. Ferreira, Mafalda Galhardo, João M. Nogueira

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 25, 2025

Aging is characterized by changes in gene expression, some of which can drive deleterious cellular phenotypes and senescence. The transcriptional activation senescence genes has been mainly attributed to epigenetic shifts, but the chromatin accessibility its underlying mechanisms remain largely elusive natural aging. Here, we profiled human dermal fibroblasts (HDFs) from individuals with ages ranging neonatal octogenarian. We found that AP-1 binding motifs are prevalent elderly-specific accessible regions while neonatal-specific highly enriched for TEAD motifs. further show TEAD4 FOXM1 share a conserved regulatory landscape controlled not previously described age-dependent enhancer loses aging whose deletion drives Finally, demonstrate ectopic expression elderly cells partially resets youthful state due FOXM1's repressive function on several members complex, known trigger program. These results place at top hierarchical level remodeling required prevent Loss activity play key role authors repression AP-1-linked opening governs identify cis elements behind downregulation

Language: Английский

Citations

0
Computational tools for inferring transcription factor activity DOI Creative Commons
Dennis Hecker, Michael Lauber, Fatemeh Behjati Ardakani

et al.

PROTEOMICS, Journal Year: 2023, Volume and Issue: 23(23-24)

Published: Sept. 14, 2023

Abstract Transcription factors (TFs) are essential players in orchestrating the regulatory landscape cells. Still, their exact modes of action and dependencies on other aspects remain elusive. Since TFs act cell type‐specific each TF has its own characteristics, untangling interactions from an experimental point view is laborious convoluted. Thus, there ongoing development computational tools that estimate transcription factor activity (TFA) a variety data modalities, either based mapping to putative target genes or genome‐wide, gene‐unspecific fashion. These can help gain insights into regulation prioritize candidates for validation. We want give overview available TFA, illustrate examples application, debate common result validation strategies, discuss assumptions concomitant limitations.

Language: Английский

Citations

9
NK Cell–Monocyte Cross-talk Underlies NK Cell Activation in Severe COVID-19 DOI Creative Commons
Madeline Lee, Izumi de los Rios Kobara, Trisha R. Barnard

et al.

The Journal of Immunology, Journal Year: 2024, Volume and Issue: 212(11), P. 1693 - 1705

Published: April 5, 2024

Abstract NK cells in the peripheral blood of severe COVID-19 patients exhibit a unique profile characterized by activation and dysfunction. Previous studies have identified soluble factors, including type I IFN TGF-β, that underlie this dysregulation. However, role cell–cell interactions modulating cell function during remains unclear. To address question, we combined communication analysis on existing single-cell RNA sequencing data with vitro primary coculture experiments to dissect mechanisms underlying dysfunction COVID-19. We found are predicted interact most strongly monocytes occurs via both factors direct interactions. validate these findings, performed cocultures which from healthy human donors were incubated COVID-19+ or donors. Coculture recapitulated aspects phenotype observed COVID-19, decreased expression NKG2D, increased markers, proliferation. When Transwell setting, only CD56bright CD16− activated presence patient monocytes. O-link supernatants revealed cultures containing had significantly elevated levels proinflammatory cytokines chemokines, as well TGF-β. Collectively, results demonstrate between contribute

Language: Английский

Citations

2
Distinct tumor-TAM interactions in IDH-stratified glioma microenvironments unveiled by single-cell and spatial transcriptomics DOI Creative Commons
Meysam Motevasseli, Maryam Darvishi, Alireza Khoshnevisan

et al.

Acta Neuropathologica Communications, Journal Year: 2024, Volume and Issue: 12(1)

Published: Aug. 16, 2024

Tumor-associated macrophages (TAMs) residing in the tumor microenvironment (TME) are characterized by their pivotal roles progression, antitumor immunity, and TME remodeling. However, a thorough comparative characterization of tumor-TAM crosstalk across IDH-defined categories glioma remains elusive, likely contributing to mixed outcomes clinical trials. We delineated phenotypic heterogeneity TAMs IDH-stratified gliomas. Notably, two TAM subsets with mesenchymal phenotype were enriched IDH-WT glioblastoma (GBM) correlated poorer patient survival reduced response anti-PD-1 immune checkpoint inhibitor (ICI). proposed SLAMF9 receptor as potential therapeutic target. Inference gene regulatory networks identified PPARG, ELK1, MXI1 master transcription factors BMD-TAMs. Our analyses reciprocal interactions revealed distinct tumors, including ANXA1-FPR1/3, FN1-ITGAVB1, VEGFA-NRP1, TNFSF12-TNFRSF12A known contribution immunosuppression, proliferation, invasion recruitment. Spatially resolved transcriptomics further elucidated architectural organization highlighted communications. Furthermore, we demonstrated significant upregulation ANXA1, FN1, NRP1, TNFRSF12A genes tumors using bulk RNA-seq RT-qPCR. Longitudinal expression analysis candidate no difference between primary recurrent indicating that interactive network malignant states does not drastically change upon recurrence. Collectively, our study offers insights into unique cellular composition communication TME, revealing novel vulnerabilities for interventions GBM.

Language: Английский

Citations

2