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Expression in irradiated MEFs exposed to murine acute lymphoblastic leukemia cells

ABSTRACT: Primary pre-B acute lymphoblastic (ALL) cells do not proliferate long-term ex vivo without the presence of stromal support. We developed and use an ex vivo co-culture model, consisting of mouse leukemic pre-B Bcr/Abl-expressing ALL cells grown with mitotically inactivated mouse embryonic fibroblasts (MEFs). This system provides a generic type of environmentally-mediated protection to the ALL cells, because when the ALL cells are treated with a moderate dose of a therapeutic drug, drug-resistant ALL cells can be recovered after a 1-2 week period of culture. Some of the factors produced by stromal cells that provide protection to ALL cells have been identified. However, it is unclear if the presence of drug-treated ALL cells affects the stromal fibroblasts. The current study was initiated to examine this using expression profiling on the irradiated MEFs. We isolated RNA from irradiated wild-type MEFs after a 9-day culture period. MEFs had either been exposed to DMSO, to nilotinib, a drug that is not expected to affect them, or to ALL cells treated with DMSO or nilotinib. MEFs and ALL cells were physically separated by a Transwell membrane of a pore size that did not allow the ALL cells to migrate towards the MEFs, but allowed the exchange of diffusible molecules.

ORGANISM(S): Mus musculus

SUBMITTER: Nora Heisterkamp

PROVIDER: E-GEOD-33329 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Expression in irradiated MEFs exposed to murine acute lymphoblastic leukemia cells

Project description:Primary pre-B acute lymphoblastic (ALL) cells do not proliferate long-term ex vivo without the presence of stromal support. We developed and use an ex vivo co-culture model, consisting of mouse leukemic pre-B Bcr/Abl-expressing ALL cells grown with mitotically inactivated mouse embryonic fibroblasts (MEFs). This system provides a generic type of environmentally-mediated protection to the ALL cells, because when the ALL cells are treated with a moderate dose of a therapeutic drug, drug-resistant ALL cells can be recovered after a 1-2 week period of culture. Some of the factors produced by stromal cells that provide protection to ALL cells have been identified. However, it is unclear if the presence of drug-treated ALL cells affects the stromal fibroblasts. The current study was initiated to examine this using expression profiling on the irradiated MEFs.

2011-12-01 | GSE33329 | GEO

Taurine ameliorates oxidative stress of BMSCs and promotes osteogenesis in irradiated jaws

Project description:Osteoradionecrosis of the jaw (ORNJ) is a complication after head and neck radiotherapy that severely affects patients’ quality of life. Currently, an overall understanding of microenvironmental factors of ORNJ is still lacking. Here, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells with scRNA-Seq and the decrease of taurine in irradiated bone marrow mesenchymal stromal cells (BMSCs) with metabolomics. Compared to the unirradiated BMSCs, the taurine uptake of irradiated BMSCs increases. The taurine concentration in peripheral blood and jaws of irradiated mice are significantly lower than the unirradiated mice. Supplementation of taurine promotes osteogenic differentiation, decreases oxidative stress and DNA damage of irradiated BMSCs. Oral administration of taurine significantly promotes survival rate of irradiated mice and promotes osteogenesis of irradiated jaws. Our study sheds light on the role of taurine during the recovery of radiation-induced jaw injury, suggesting a potential non-invasive therapeutic means to combat ORNJ.

2024-07-08 | MTBLS10284 | MetaboLights

Microarray analysis of gene expression in mouse embryonic fibroblasts (MEFs) by addition of serum from L/MDR irradiated mice at 10 and 20 days.

Project description:The expression changes were detected by addition of serum form L/MDR irradiated mice at 10 and 20 days in mouse embryonic fibroblasts (MEFs). (Expression of MEFs by addition of serum from nonirradiated mice) vs (Expression of MEFs by addition from L/MDR irradiated mice)

2013-12-31 | E-GEOD-37958 | biostudies-arrayexpress

Transcriptional Mediator Subunit MED1/TRAP220 in Stromal Cells Is Involved in Hematopoietic Stem/Progenitor Cell Support through Osteopontin Expression

Project description:MED1/TRAP220, a subunit of the transcriptional Mediator/TRAP complex, is crucial for various biological events through its interaction with distinct activators such as nuclear receptors and GATA family activators. In hematopoiesis, MED1 plays a pivotal role in optimal nuclear receptor-mediated myelomonopoiesis and GATA-1-induced erythropoiesis. In this study, we present evidence that MED1 in stromal cells is involved in supporting hematopoietic stem and/or progenitor cells (HSPCs) through osteopontin (OPN) expression. We found that the proliferation of bone marrow (BM) cells cocultured with MED1 knockout (Med1-/-) mouse embryonic fibroblasts (MEFs) was significantly suppressed when compared to the control. Furthermore, the number of long-term culture-initiating cells (LTC-ICs) was attenuated for BM cells cocultured with Med1-/- MEFs. The vitamin D receptor (VDR)- and Runx2-mediated expression of OPN, as well as Mediator recruitment to the Opn promoter, was specifically attenuated in the Med1-/- MEFs. Addition of OPN to these MEFs restored the growth of cocultured BM cells and the number of LTC-ICs, both of which were attenuated by the addition of the anti-OPN antibody to Med1+/+ MEFs and to BM stromal cells. Consequently, MED1 in niche appears to play an important role in supporting HSPCs, by upregulating VDR- and Runx2-mediated transcription on the Opn promoter. Total RNAs of mouse embryonic fibroblasts (MEFs) derived from Med1-/-/p53-/- and Med1+/+/p53-/- E10.0 embryos were compared. Duplicate samples for each MEF type were analyzed.

2010-08-31 | E-GEOD-22471 | biostudies-arrayexpress

Mus musculus

Project description:Drug tolerance development of mouse Bcr/Abl pre-B ALL cells on irradiated MEFs

| PRJNA159405 | ENA

Extensive protein group SUMO modification of repressive chromatin factors distinguishes pluripotent from somatic cells

Project description:Post-translational modification by SUMO is a key regulator of cell identity. In mouse embryonic fibroblasts (MEFs), SUMO impedes reprogramming to pluripotency, while in embryonic stem cells (ESCs), it represses the emergence of totipotent-like cells, suggesting that SUMO targets distinct substrates to preserve somatic and pluripotent states. Using MS-based proteomics, we show that the composition of endogenous SUMOylomes differs dramatically between MEFs and ESCs. In MEFs, SUMO2/3 targets proteins associated with canonical SUMO functions, such as splicing, and transcriptional regulators driving somatic enhancer selection. In contrast, in ESCs, SUMO2/3 primarily modifies highly interconnected repressive chromatin complexes, thereby preventing chromatin opening and transitioning to totipotent-like states. We also characterize several SUMO-modified pluripotency factors and show that SUMOylation of Dppa2 and Dppa4 impedes the conversion to 2-cell-embryo-like states. Altogether, we propose that rewiring the repertoire of SUMO target networks is a major driver of cell fate decision during embryonic development.

2020-09-16 | PXD017697 | Pride

Extensive protein group SUMO modification of repressive chromatin factors distinguishes pluripotent from somatic cells (total proteome)

2020-09-16 | PXD020287 | Pride

Microarray analysis of gene expression in ATM-deficient MEFs

Project description:The expression of interferon-related genes was more enhanced in irradiated ATM-deficient mouse embryonic fibroblasts (MEFs) than in irradiated ATM wild-type MEFs.

2012-06-20 | GSE23116 | GEO

E-GEOD-37286

Project description:Drug tolerance development of mouse Bcr/Abl pre-B ALL cells on irradiated MEFs

2015-09-28 | E-GEOD-37286 | ExpressionAtlas

Expression data from MEFs wt cells starved as compared to MEFs wt cells grown in Normal Medium

Project description:In order to identify the effects of starvation on the MEFs wt trascriptome, we performed Affymetrix Gene-Chip hybridization experiments for the starved cells Transcriptome analysis of the starved MEFs wt cells For the analysis on the starved MEFs wt cells, total RNA was extracted; RNA extracted from MEFs wt cells grown in Normal Medium was used as control

2015-02-24 | E-GEOD-56671 | biostudies-arrayexpress

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