Transcriptomics modification consecutive to AS1842856 treatment in primary T lymphocytes
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ABSTRACT:
PROVIDER: PRJNA515876 | ENA |
REPOSITORIES: ENA
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Project description:We have observed that the FOXO1 inhibitor AS1842856 induces a significant increase of both the bioenergetics and transcriptional activity of human T cells, together with a significant increase in their size, without any cell division. These modifications are accompanied by a decrease of p27 expression, contrasting with an increase of CDK2 cellular levels and by the phosphorylation of Rb and SAMHD1 proteins. As these changes are known to be characteristic of cells undergoing a G0 to G1 progression. To get an overall view of these changes in T-cell metabolism, we performed gene expression microarray analysis of PBT cultured during 7 days in the presence or not of AS1842856. We conclude that inhibition of FOXO1 by AS1842856 is sufficient to induce a profound reprogramming of human T lymphocytes, regulating their exit from quiescence.
2019-03-08 | GSE125328 | GEO
Project description:In 10X Genomics Visium Spatial Gene Expression (ST), the resolution for distinguishing neighboring cells can be improved using data integration with single-cell/single-nuclei transcriptomics profiles. Besides, depending on the cell type and tissue, nuclei size may vary significantly to an extent that it may exceed the thickness of tissue slices. This may jeopardize capturing full transcriptomics profile of single slice due to the improper/incomplete incision of nuclei during cryosectioning process and this may cause drawbacks in downstream analysis. To monitor the probable consequences, we monitored the effect of consecutive slices data integration (CSDI) on improvement of cell type clustering and annotation through transferring cell labels from a single-nuclei transcriptomics dataset to ST. To do so, two consecutive slices from the orbitofrontal neocortex and temporal neocortex of two post mortem brain samples were obtained and their spatial transcriptomics profiles were retrieved using 10x Genomics Visium Spatial Gene Expression protocol. Using CSDI, not only the number of identified clusters were increased and the inconsistency between the pattern of clusters in consecutive slices was resolved, but the layered-structure of gray matter was unveiled. Besides, only after CSDI the transferred annotations from single-nuclei transcriptomics to ST could match the microscopic results. CSDI can improve the ST clustering and cell type annotation by providing the full signals coming from all cell types of single slice of tissue. The codes in R programming language are publicly available at https://github.com/ElyasMo/ST_snRNA-seq
2023-05-12 | GSE184510 | GEO
Project description:AS1842856 treatment in BT549 cells
| PRJNA745342 | ENA
Project description:Basal-like breast cancer (BBC) is a poor prognosis cancer that lacks effective targeted therapy. Recently our group and others found that forkhead box transcription factor FOXO1 promotes stem gene expression in BBC and GBM cell lines. Given the critical role of cancer stem cells in promoting cancer progression, we examined the impact of FOXO1 inhibition with AS1842856 on BBC cells. We treated BT549 cells with 200nM AS1842856 for 48 hours and found that FOXO1 inhibition induced a set of WNT Pathway genes.
2023-11-15 | GSE179856 | GEO
Project description:Expression profiles of seven consecutive stages of mouse thymocyte development were generated.
2007-12-20 | E-GEOD-272 | biostudies-arrayexpress
Project description:Analysis of expression quantitative trait loci (eQTLs) using RNA derived from freshly harvested peripheral blood CD4+ lymphocytes from 200 asthmatics collected in clinical settings. RNA was obtained from peripheral blood CD4+ lymphocytes at four study centers. Peripheral blood (17 cc) was collected into BD Vacutainer CPT tubes (BD Diagnostics, Franklin Lakes, New Jersey) and placed on ice. Samples were centrifuged within 1 hour of collection for 20 minutes at 1700RCF, followed by mononuclear cell layer isolation and suspension in 10 ml of PBS. We isolated CD4+ lymphocytes using anti-CD4+ microbeads by column separation (Miltenyi Biotec, Auburn, CA) using 20 µl anti-CD4+ Micro beads per 106 total cells
2010-06-23 | E-GEOD-22324 | biostudies-arrayexpress
Project description:Our study demonstrated that the expression of Igf2bp1 in activated microglia was significantly up-regulated, implying a role of Igf2bp1 in LPS-induced m6A modifications in microglia. To understand the roles of Igf2bp1 on LPS-induced m6A modification in microglia, we performed Igf2bp1 loss-of-function (LOF) approach. Microglia stimulated by LPS were transfected with either scrambled siRNA control or Igf2bp1 siRNA for 48 hours. To m6A modification profiles in control and Igf2bp1 LOF microglia were determined by MeRIP-seq analysis.
2022-12-31 | E-MTAB-11411 | biostudies-arrayexpress
Project description:Analysis of expression quantitative trait loci (eQTLs) using RNA derived from freshly harvested peripheral blood CD4+ lymphocytes from 200 asthmatics collected in clinical settings.
2010-06-14 | GSE22324 | GEO
Project description:Activation of the transcription factor FOXO1 contributes to multiple pathological processes. The FOXO1 inhibitor AS1842856 demonstrated strong therapeutic effects in pre-clinical models of common diseases like diabetes and anthracyclines-induced heart failure. We have previously identified FOXO1 as a B-ALL dependency and demonstrated in in vivo B-ALL models that AS1842856 increased the survival and decreased B-ALL tumor load in all critical organ compartments, but most efficiently in the CNS. Here, we interrogated the underlying molecular mechanisms by comparison of the transcriptomic effects of AS1842856 and Foxo1-KO in a B-ALL mouse model. Despite the significant similarity in sets of regulated genes, we identified GSK3B inhibition as a signature enriched only in AS1842856-treated cells. Using an in vitro kinase assay, we identified AS1842856 as a direct GSK3B inhibitor that ultimately stabilizes CTNNB1. CTNNB1-KO partially protected B-ALL cell lines from the cytotoxic effect of AS1842856. At the same time, using a chemical protein degradation model, we found that FOXO1 indeed contributes to the cytotoxic effect of AS1842856. We conclude that AS1842856 targets two known B-ALL vulnerabilities: GSK3B and FOXO1. The unique mode of action, low toxicity, and ability to penetrate the blood-brain barrier warrant further investigation of the therapeutic potential of AS1842856 in B-ALL.
2025-07-23 | GSE283254 | GEO