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Precision rescue of SP140 SNP+/+ Crohn's disease patient peripheral blood mononuclear cells responses to lipopolysaccharide using topoisomerase I or II inhibitors

ABSTRACT: Peripheral blood-derived mononuclear cells isolated from Crohn's disease patients were pretreated with DMSO control, topotecan and etoposide and stimulated with LPS for 4 hours.

ORGANISM(S): Homo sapiens

PROVIDER: GSE161031 | GEO | 2020/12/03

REPOSITORIES: GEO

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Precision rescue of SP140 SNP+/+ Crohn's disease patient peripheral blood mononuclear cells responses to lipopolysaccharide using topoisomerase I or II inhibitors

Project description:Precision rescue of SP140 SNP+/+ Crohn's disease patient peripheral blood mononuclear cells responses to lipopolysaccharide using topoisomerase I or II inhibitors

| PRJNA675222 | ENA

Co-ordinate inhibition of autism candidate genes by topoisomerase inhibitors [Seq]

2013-08-30 | E-GEOD-43526 | biostudies-arrayexpress

Co-ordinate inhibiton of autism candidate genes by topoisomerase inhibitors [array]

Project description:Topoisomerases are necessary for the expression of neurodevelopmental genes, and are mutated in some patients with autism spectrum disorder (ASD). We have studied the effects of inhibitors of Topoisomerase 1 (Top1) and Topoisomerase 2 (Top2) enzymes on mouse cortical neurons. We find that topoisomerases selectively inhibit long genes (>100kb), with little effect on all other gene expression. Using ChIPseq against RNA Polymerase II (Pol2) we show that the Top1 inhibitor topotecan blocks transcriptional elongation of long genes specifically. Many of the genes inhibited by topotecan are candidate ASD genes, leading us to propose that topoisomerase inhibition might contribute to ASD pathology. 9 experiments, gene expression measured by Affymetrix microarray. 1) cultured mouse cortical neurons treated with 300nM topotecan vs vehicle-treated controls 2) cultured mouse neurons treated with 1uM topotecan vs vehicle-treated controls 3) cultured mouse cortical neurons treated with 3uM ICRF-193 vs vehicle-treated controls. 4) cultured mouse cortical neurons treated with 10 uM irinotecan vs vehicle-treated controls. 5) cultured mouse cortical neurons treated with 3-1000 nM topotecan vs vehicle treated controls 6) cultured mouse cortical neurons treated with lentivirus expressing shRNA against Top1 and Top2b vs scrambled shRNA controls 7) cultured mouse cortical neurons treated with DRB vs vehicle-treated controls 8) cultured mouse cortical neurons treated with hydrogen peroxide or paraquat vs vehicle-treated controls 9) cultured mouse cortical neurons treated with topotecan with or without subsequent drug washout, vs vehicle-treated controls.

2013-08-30 | E-GEOD-43899 | biostudies-arrayexpress

Colonic Crohn's left and right colon

Project description:Colonic Crohn's Disease from a single patient in remission with mild disease index

2020-08-24 | GSE141553 | GEO

Fibrotic signatures in Crohn's disease patients

Project description:This study investigates the presence of specific fibrosis-associated gene expression signatures in Crohn's disease patient biopsies.

2022-01-02 | GSE192786 | GEO

Transcriptomic analysis reveals the dynamic changes of immune responses during the development of creeping fat in Crohn's disease

Project description:In Crohn's disease, creeping fat is the characteristic expansion of mesenteric adipose tissue wrapping around the inflamed intestine. Through a comparative transcriptomic analysis of creeping fat and normal-looking mesenteric adipose tissues from patients with Crohn's disease and non-Crohn's disease, we found that a dynamic transcriptional and cell compositional change occurs during the progression from non-Crohn's disease to Crohn's disease, and finally to creeping fat.

2023-09-06 | GSE227376 | GEO

Myeloid-stromal subtypes reveal NOD2-mediated Crohn's and rescue pathways

Project description:Myeloid-stromal subtypes reveal NOD2-mediated Crohn's and rescue pathways

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Topoisomerase 1 Regulates Gene Expression in Neurons through Cleavage Complex-Dependent and -Independent Mechanisms

Project description:Topoisomerase 1 (TOP1) inhibitors, including camptothecin and topotecan, covalently trap TOP1 on DNA, creating cleavage complexes (cc’s) that must be resolved before gene transcription and DNA replication can proceed. We previously found that topotecan reduces the expression of long (>100 kb) genes and unsilences the paternal allele of Ube3a in neurons. Here, we sought to evaluate overlap between TOP1cc-dependent and -independent gene regulation in neurons. To do this, we utilized Top1 conditional knockout mice, Top1 knockdown, the CRISPR-Cas9 system to delete Top1, TOP1 catalytic inhibitors that do not generate TOP1cc’s, and a TOP1 mutation (T718A) that stabilizes TOP1cc’s. We found that topotecan treatment significantly alters the expression of many more genes, including long neuronal genes, immediate early genes, and paternal Ube3a, when compared to Top1 deletion. Our data show that topotecan has a stronger effect on neuronal transcription than Top1 deletion, and identifies TOP1cc-dependent and -independent contributions to gene expression.

2016-05-27 | GSE79951 | GEO

RNA-seq of 4 Crohn's disease and 4 control

Project description:mRNA-seq raw data of 4 Crohn's disease and 4 control from colon tissue

2022-01-01 | GSE164871 | GEO

Comparing Co-morbid Crohn's-Spndyloarhtritis to each of the underlying dieases

Project description:This study was carried out to determine how immunological signatures related in the colon and periperhal blood between indivudals with Crohn's, Spondyloarhtritis, and individuals with both diseases. We carried out one experiments with 1 patient in each condition (1 Crohn's, 1 Spondyloarthritis, 1 Co-morbid, 1 HC), which we then repeated for a total of 8 subjects.

2021-05-25 | GSE163314 | GEO

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