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CosMX spatial transcriptomics of mouse subcutaneous EO771 tumors to study synergistic effects of NEDD8 depletion and anti-PD-1 therapy

ABSTRACT: We have established the phenotype that depletion of NEDD8 in tumor cell has synergestic effect with anti-PD1 therapy in mouse EO771 subcutaneous tumor model. In this study we performed CosMX spatial transcriptomics of mouse tumor samples to study the tumor intrinsic and immune environment changes that could explain the outcome.

ORGANISM(S): Mus musculus

PROVIDER: GSE318797 | GEO | 2026/02/09

REPOSITORIES: GEO

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CosMX spatial transcriptomics of mouse subcutaneous EO771 tumors to study synergistic effects of NEDD8 depletion and anti-PD-1 therapy

Project description:CosMX spatial transcriptomics of mouse subcutaneous EO771 tumors to study synergistic effects of NEDD8 depletion and anti-PD-1 therapy

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Comparing the transcriptome expression differences between breast cancer cells EO771-tdT-Parental and EO771-tdT-LM2 using high-throughput sequencing.

Project description:The molecular mechanisms that regulate breast cancer cell (BCC) metastasis and proliferation within the leptomeninges (LM) are poorly understood, limiting development of effective therapies. Here we show that BCCs in mice can invade the LM by abluminal migration along blood vessels that connect vertebral/calvarial bone marrow and meninges, bypassing the blood-brain barrier. To screen for signaling pathways in EO-LM2 cells that could support their survival or proliferation in the meningeal niche, we performed RNA-seq analysis of EO771-tdT-Parental and EO771-tdT-LM2 to compare their transcriptome expression differences.

2025-04-03 | GSE263184 | GEO

RNA-seq of mouse EO771 triple-negative breast cancer model with stemness inhibitors: salinomycin, SB-431542, JIB-04, napabucasin, and their quadruple combination against an untreated control

Project description:We conducted an in vivo study of stemness inhibitors using the EO771 triple-negative breast cancer mouse model. Ten days after subcutaneous injection of 1 million of EO771 cells into 8-12 week C57BL/6 female mice right flank, tumors reached around 100-200 mm³. Each treatment group (n=2-3 per group) received three doses of stemness inhibitors (every 3 days) in monotherapy (A - salinomycin, B - SB-431542, C - JIB-04, D - napabucasin) or combination therapy (ABCD). Control mice were left untreated. Tumors were harvested one day after the last treatment and subjected to bulk RNA-seq. This study aims to identify if treatment with stemness inhibitors affected the immune tumor microenvironment in this model.

2025-03-12 | E-MTAB-14915 | biostudies-arrayexpress

E2-RING expansion of the NEDD8 cascade confers specificity to cullin modification

Project description:Ubiquitin and ubiquitin-like proteins (UBLs) are directed to targets by cascades of E1, E2, and E3 enzymes. The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2). CRLs are activated by ligation of the UBL NEDD8 to a conserved cullin lysine. How is cullin NEDD8ylation specificity established? Here we report that, like UBE2M (also known as UBC12), the previously uncharacterized E2 UBE2F is a NEDD8-conjugating enzyme in vitro and in vivo. Biochemical and structural analyses indicate how plasticity of hydrophobic E1-E2 interactions and E1 conformational flexibility allow one E1 to charge multiple E2s. The E2s have distinct functions, with UBE2M/RBX1 and UBE2F/RBX2 displaying different target cullin specificities. Together, these studies reveal the molecular basis for and functional importance of hierarchical expansion of the NEDD8 conjugation system in establishing selective CRL activation. Mol Cell 33:483-495, 2009. Keywords: Comparison of gene expression profiles Ube2m and Ube2f are E2 enzymes that direct protein modification by NEDD8. Here we explore the specific functions of Ube2f and Ube2m by comparing gene expression profiles following knockdown of their function in NIH 3T3 cells. We used microarrays to detail the global programme of gene expression changes following knockdown of Ube2m and Ube2f in NIH 3T3 cells. NIH 3T3 cells were transduced with retroviral constructs containing shRNA directed against Ube2m or Ube2f. Three replicates of each condition were analyzed.

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Comparison of LPS-induced gene expression in NEDD8-sufficient or -deficient primary macrophages

Project description:Bone marrow-derived macrophages (BMMs) from Nedd8(flox/flox) mice or Nedd8(flox/flox; lyz2-cre) mice were stimulated with or without 100ng/ml LPS for 4 hours. The total RNA was prepared and subjected to microarray.

2020-05-26 | GSE99386 | GEO

Bulk RNA-seq of EO771 tumor sample Gq_DREADD vs. Ctr

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2026-06-18 | GSE309464 | GEO

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NanoString CosMx SMI (human) on ten human MASLD samples

Project description:CosMx SMI is a high-plex in situ analysis platform to provide spatial multiomics with formalin-fixed paraffin-embedded (FFPE) and fresh frozen (FF) tissue samples at cellular and subcellular resolution. CosMx SMI is an integrated system with mature cyclic fluorescent in situ hybridization (FISH) chemistry, high-resolution imaging readout, interactive data analysis and visualization software. Herein we used the CosMx SMI with the CosMxTM Human Universal Cell Characterization RNA Panel (1000-plex) supplemented with 14 custom genes of interest to probe different disease stages of MASLD/MASH, previously known as NAFLD.

2025-12-18 | GSE312698 | GEO

Comparison of gene expression in NEDD8-sufficient or -deficient neonatal liver

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2022-06-24 | GSE133215 | GEO

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2025-10-03 | GSE308146 | GEO

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