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A polycomb-independent role of EZH2 in TGFβ1-damaged epithelium triggers a fibrotic cascade with mesenchymal cells

ABSTRACT: We sequenced mRNA from A549 and NHLFs in mono-culture and co-culture system that had been subjected to 1 ng/ml TGFß1 apically for 72h. Vehicle (HCl/BSA) treatment was used as control. 4 biological replicates for each condition.

ORGANISM(S): Homo sapiens

PROVIDER: GSE155832 | GEO | 2020/12/31

REPOSITORIES: GEO

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TGFβ1-mediated functional inhibition of mesenchymal stromal cells in MDS and AML

Project description:Mesenchymal stromal cells (MSC) are involved in the pathogenesis of myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), but how they contribute to the expansion of malignant cells and hematopoietic failure is poorly understood. To further characterize the pathological phenotype we performed RNA sequencing of MSC from patients with MDS and AML. Data analysis revealed a specific molecular signature with a significant overlap of genes commonly deregulated in all MDS subtypes and in AML. Pathway analysis revealed a strong enrichment of genes related to osteogenesis, senescence, inflammatory processes and inhibitory cytokines thereby reflecting the structural and functional deficits of MDS- and AML-derived MSC on a molecular level. Further analysis identified TGFß1 as the most probable extrinsic trigger factor for this altered gene expression. Following exposure to TGFß1 healthy MSC adopted a phenotype reminiscent of that observed in primary patient-derived MSC which was characterized by impaired growth potential, osteogenic differentiation capacities, a specific gene expression profile and diminished stromal hematopoietic support. These suppressive effects of TGFß1 on MSC functionality were abrogated by SD-208, an established inhibitor of TGFß receptor signalling. Blockade of TGFß signalling by SD-208 also restored the osteogenic differentiation capacity of patient-derived MSC, thus confirming the role of TGFß1 in the bone marrow microenvironment of patients with MDS and AML. Our findings establish TGFß1 as a relevant trigger causing functional inhibition of MSC in MDS and AML and identify SD-208 as a candidate for the reversal of these effects

2018-11-29 | GSE107490 | GEO

H. sapiens First trimester placental villous explant 0conditioned media; galectin-7/BSA treatment; 2% O2

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2021-04-20 | PXD019331 | Pride

A polycomb-independent role of EZH2 in TGFβ1-damaged epithelium triggers a fibrotic cascade with mesenchymal cells

Project description:A polycomb-independent role of EZH2 in TGFβ1-damaged epithelium triggers a fibrotic cascade with mesenchymal cells

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Effects of LMTK2 knockdown on total RNA expression in CFBE41o- cells after TGFβ1 or vehicle control (HCl+BSA) treatment

Project description:Effects of LMTK2 knockdown on total RNA expression in CFBE41o- cells after TGFβ1 or vehicle control (HCl+BSA) treatment

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Expression data from adult rat subventricular zone cells

Project description:Transforming growth factor (TGF)-ß1 is a multifunctional cytokine regulating a number of physiological and patho-physiological processes in the adult brain. Its expression is elevated during neurodegeneration, which is associated with reduced levels of neurogenesis. We have postulated that TGF-ß1 might be one of the crucial factors involved in limiting neurogenesis in the diseased brain. We used microarrays to detail the gene expression profile after TGFbeta-1 treatment and identified distinct classes of up- and downregulated genes. Keywords: control versus TGFbeta1 treated group Adult rat subventricular zone cells were cultured for 7 days under proliferation conditions. Control cells were exposed to HCl/BSA whereas TGFbeta-1 treated cells received 10 ng/ml TGFbeta-1 dissolved in HCl/BSA 3 times per week. RNA was extracted followed by hybridization on Affymetrix microarrays.

2011-05-10 | E-GEOD-14556 | biostudies-arrayexpress

Expression data from adult rat subventricular zone cells

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Braf inhibitors reverse the unique molecular signature and phenotype of hairy cell leukemia, and exert anti-leukemic activity

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2014-12-12 | GSE63790 | GEO

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2011-02-17 | E-GEOD-27350 | biostudies-arrayexpress

Identification of genes responsive to change in apical polarity in the breast epithelium

Project description:Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis, except during the early stages of cancer development. Using mammary glandular structures (acini) produced in a three-dimensional cell culture system we have demonstrated that, in order for mammary epithelial cells to exit quiescence and enter the cell cycle, acini have to lose apical polarity. In order to identify the genes dependent on apical polarity that could control cell quiescence, and possibly other aspects of tissue homeostasis, we have used Affymetrix technology microarray analysis of the 22,277 features/genes of the Human Genome U133A 2.0 array Chip in apically polarized and non-polarized breast epithelial acinar cells in three-dimensional culture. Genes commonly down-regulated in two treatments that altered apical polarity compared to control were considered to be dependent on apical polarity status for their transcription. Apically polarized (Control) and two different populations of non-polarized human mammary epithelial cells (18-alpha-glycyrrhetinic acid =AGA, and 5-aza-2'-deoxycytidine =Aza) were used for microarray analysis containing four biological replicates (1-4) for each treatment. The two treatments that cause loss of apical polarity were compared to reference apically polarized control samples using two different statistical analysis methods (FDR and HolmM-bM-^@M-^Ys).

2012-02-29 | E-GEOD-35165 | biostudies-arrayexpress