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Myeloma-modified 3T3-L1 adipocytes exhibit aberrant gene expression profiles [experiment 1]

ABSTRACT: Herein we compare mouse 3T3-L1 adipocyte gene expression after 7 days of adipogenic differentiation with and without exposure to MM.1S myeloma cells. Microarray analysis was used to compare adipogenic gene expression either following exposure to MM.1S cells prior to differentiation (48h) or after differentiation (72h).

ORGANISM(S): Mus musculus

PROVIDER: GSE143267 | GEO | 2021/03/10

REPOSITORIES: GEO

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Myeloma-modified 3T3-L1 adipocytes exhibit aberrant gene expression profiles [experiment 2]

Project description:Herein we compare mouse 3T3-L1 adipocyte gene expression after 7 days of adipogenic differentiation with and without exposure to MM.1S myeloma cells. Microarray analysis was used to compare adipogenic gene expression either following exposure to MM.1S cells prior to differentiation (48h) or after differentiation (72h).

2020-11-01 | GSE143268 | GEO

Myeloma-modified adipocytes exhibit a senescent-associated secretory phenotype

Project description:Bone marrow -adipocytes (BMAs) have recently been implicated in accelerating bone metastatic cancers such as AML and breast cancer. Importantly, bone marrow adipose tissue (BMAT) expands with aging and obesity- two key risk factors in multiple myeloma (MM) disease prevalence- suggesting that BMAs influence and are influenced by myeloma cells in the marrow. Here we examined how myeloma cells affect adipocytes and provide evidence that MM cells alter adipocyte gene expression and cytokine secretion profiles, creating a “MM-associated” adipocyte (MM-adipocyte) phenotype. Our findings indicate that: (1) Multiple myeloma cells decrease BM adiposity in vitro, in myeloma animal models, and in clinical samples, (2) myeloma induces widespread gene expression and phenotypic changes in adipocytes in vitro, most notable, the induction of a senescent-like phenotype in BMAs, (3) MM-adipocytes affect myeloma cell cycle, drug sensitivity, and aggressiveness, illuminating a new driver of MM cell evolution in a drug resistant clone. We demonstrate that myeloma cells exposed to MM-adipocytes are rescued from dexamethasone-induced cell cycle arrest and have increased expression of FKBP5, a potential drug resistance gene. Our findings in patients confirm that BMAs are dynamic during myeloma disease progression (decrease during MM initiation, recover during disease remission) and that the interactions between BMAs and MM cells have previously unappreciated implications in the understanding and treatment of myeloma.

2021-03-10 | GSE140374 | GEO

Myeloma-modified 3T3-L1 adipocytes exhibit aberrant gene expression profiles

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-11-01 | GSE143269 | GEO

RNAseq analysis of 3T3-L1 adipocytes cultured in high and low media volumes

Project description:3T3-L1 fibroblasts were cultured in high glucose DMEM supplemented with 10% foetal bovine serum (FBS) and 2 mM glutamax at 37°C in 10% CO2. For differentiation into adipocytes, fibroblasts were seeded into 12-well plates, and cultured in 1 mL/well of 10% FBS-supplemented DMEM containing an adipogenic cocktail (350 nM insulin, 0.5 mM 3-isobutyl-1-methylxanthine, and 250 nM dexamethasone) for 3 d, followed by 3 d in DMEM containing 10% FBS and 350 nM insulin. On day 9 post-differentiation, media volumes were either kept at 1 mL (high) or switched to 0.33 mL (low) for 16 h. Cells were then lysed in 350 µL RLT buffer for RNA extraction and sequencing.

2023-10-01 | E-MTAB-12298 | biostudies-arrayexpress

The Differentiation and Stress Response Factor, XBP-1, Drives Multiple Myeloma Pathogenesis

Project description:Multiple myeloma (MM) evolves from highly prevalent premalignant condition termed Monoclonal Gammopathy of Undetermined Significance (MGUS). We report an MGUS-MM phenotype arising in transgenic mice with Emu-directed expression of the unfolded protein/ER stress response and plasma cell development spliced isoform factor XBP-1s. Emu-XBP-1s elicited elevated serum Ig and IL-6 levels, skin alterations and with advancing age, a significant proportion of Emu-xbp-1s transgenic mice develop features diagnostic of human MM including bone lytic lesions. Transcriptional profiles of Emu-xbp-1s B lymphoid and MM cells show aberrant expression of genes known to be dysregulated in human MM including Cyclin D1, MAF, MAFB, and APRIL. This genetic model coupled with documented frequent XBP-1s overexpression in human MM serve to implicate chronic XBP-1s dysregulation in the development of this common and lethal malignancy. Keywords: XBP-1, MGUS, multiple myeloma, transgenic mouse

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Chromatin analysis of multiple myeloma cells following CBP/p300 inhibition and degradation (ChIP-Seq)

Project description:We performed H3K27ac ChIP-seq on MM.1S cells treated with A-485, GNE-781, and the combination of both, or with dCBP-1, and CBP & p300 ChIP on MM.1S cells.

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Differentiating 3T3-L1 adipocytes, introduced with siRNA against phf21a gene

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2012-04-04 | E-GEOD-18599 | biostudies-arrayexpress

Development of gene expression signatures for contact-inhibited and adipogenic-differentiated 3T3-L1 and NIH3T3 fibroblasts

Project description:Given previous works showing that, in the process of adipogenic differentiation of 3T3-L1 fibroblasts, the cells need to be cultured to confluency followed by additional incubation before initiating differentiation, we hypothesized that contact inhibition of proliferation (CIP) is requisite for making the cells prone to the differentiation. We screened upregulated genes in contact-inhibited 3T3-L1 fibroblasts, as well as NIH3T3 fibroblasts that are also sensitive to contact inhibition, by a whole genome microarray analysis. We also screened the genes that undergo rapid downregulation after the initiation of adipogenic differentiation. To investigate the mechanism of contact inhibition of proliferation and adipogenic differentiation of 3T3-L1 and NIH3T3 fibroblasts, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish proliferating and contact-inhibited cells and cells that undergo adipogenic differentiation. Total RNAs from 80% confluent (3T3-L1_80%, NIH3T3_80%) and overconfluent (3T3-L1_overconfluent, NIH3T3_overconfluent) cells and cells stimulated with the adipogenic differentiation medium (ZenBio) for 2 hours (3T3-L1_adipo diff med 2 hours, NIH3T3_adipo diff med 2 hours) were harvested and subjected to the microarray analysis.

2015-05-28 | E-GEOD-69320 | biostudies-arrayexpress

ZEB1 in 3T3-L1 differentiation (RNA-seq)

Project description:We aimed to characterise genome-wide gene expression changes upon ZEB1 knockdown in 3T3-L1 cells at distinct timepoints of adipogenic differentiation (days 0 and 2), performing replicate experiments.

2014-09-17 | E-MTAB-2538 | biostudies-arrayexpress

Proteasome inhibition silences oncogenic transcripts in multiple myeloma through HDAC3-mediated DNA condensation and gene relocation [CUT&RUN]

Project description:This study provides a genome-wide map of changes in degradative ubiquitination in response to proteasome inhibition in the multiple myeloma cell line MM.1S. Following proteasome inhibition with lactacystin, CUT and RUN assays were carried out to determine the genomic locations of ubiquitin in multiple myeloma cells stably expressing a flagged version of ubiquitin (MM.1S-3XFlag Ubiquitin cells). In addition, we report the DNA binding locations of the transcription factor c-MYC in basal conditions in MM.1S parental cells.

2022-11-21 | GSE193302 | GEO

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