Identification of PU. 1 target genes in mouse developing pro-B cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE87315 | GEO | 2016/12/16
SECONDARY ACCESSION(S): PRJNA344314
REPOSITORIES: GEO
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Project description:We examined the genomic PU.1 binding profile in mouse developing pro-B cells by using chromatin immunoprecipitation following high-throughput sequencing (ChIP-seq). Our goal was to determine the genes regulated by PU.1 specifically at the pro-B cell stage in B cell development.
2016-12-16 | GSE87314 | GEO
Project description:PU.1 is a key transcription factor for macrophage differentiation. Novel PU.1 target genes were identified by mRNA profiling of PU.1-deficient progenitor cells (PUER) before and after PU.1 activation. We used two different types of Affymetrix DNA-microarrays (430 2.0 arrays and ST 1.0 exon arrays) to characterize the global PU.1-regulated transcriptional program underlying the early processes of macrophage differentiation. Keywords: time course Uninduced and 24h 4-hydroxy-tamoxifen (OHT) induced PUER cells were cultured before RNA extraction and hybridization on Affymetrix Mouse Genome 430 2.0 and Mouse Exon ST 1.0 microarrays. Triplicates before (0h) and after (24h) induction of PU.1 were analyzed.
2008-10-11 | E-GEOD-13125 | biostudies-arrayexpress
Project description:PU.1 is a key transcription factor for macrophage differentiation. Novel PU.1 target genes were identified by mRNA profiling of PU.1-deficient progenitor cells (PUER) before and after PU.1 activation. We used two different types of Affymetrix DNA-microarrays (430 2.0 arrays and ST 1.0 exon arrays) to characterize the global PU.1-regulated transcriptional program underlying the early processes of macrophage differentiation. Keywords: time course
2008-10-11 | GSE13125 | GEO
Project description:Identification of CITED2 and PU.1 target genes in human CB
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Project description:Identification of PU. 1 target genes in mouse developing pro-B cells
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Project description:CB CD34+ cells were isolated by Miltenyi miniMACS column. Cells were prestimulated in HPGM with 100 ng/ml KITL, FLT3L and TPO for 12 hrs. Cells were transduced with control, CITED2 overexpression lentivectors, shRNA PU.1 lentivectors or both, in two rounds over 48 hrs. Transduced cells were sorted after which RNA was isolated for Illumina beadchip arrays HT12 v4
2019-04-17 | GSE118036 | GEO
Project description:Downregulation of the hematopoietic transcription factor PU.1 in PU.1 low acute myeloid leukemia cells (AML) by novel heterocyclic diamidines or PU.1 inhibitors leads to decrease cell proliferation and apoptosis, representing a new therapeutic strategy for AML treatment. These inhibitors induces decreased PU.1 binding on its target sites, as well as deregulation in PU.1 canonical target genes We used microarray to identify the pathways deregulated after drug treatment.
2017-12-07 | GSE77651 | GEO
Project description:Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix which lead to scaring and organ failure. In sharp contrast, the hallmark feature of fibroblasts in arthritis is matrix degradation by the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms driving these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts are enigmatic. We have compared resting, fibrotic, and inflammatory fibroblasts; PU.1 was overexpressed in dermal fibroblasts and compared to scr-transfected controls. Fibrotic fibroblasts isolated from the skin of patients with systemic sclerosis were treated with PU.1 inhibitor and compared to untreated fibrotic fibroblasts and respective healthy controls. Through this, we identified the transcription factor PU.1 as an essential orchestrator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms which normally control PU.1 expression is perturbed in fibrotic diseases such as pulmonary fibrosis, systemic sclerosis, liver cirrhosis, kidney fibrosis and chronic graft-versus-host disease, resulting in upregulation of PU.1, the induction of fibrosis-associated gene sets, and a phenotypic switch in matrix-producing pro-fibrotic fibroblasts. In contrast, inactivation of PU.1 disrupts the fibrotic network and enables re-programming of fibrotic fibroblasts into resting fibroblasts with regression of fibrosis in different organs. Targeting of PU.1 may thus represent a novel therapeutic approach for the treatment of a wide range of fibrotic diseases.
2018-11-09 | GSE122334 | GEO
Project description:More than forty loci contribute to genetic risk for Alzheimer’s disease (AD). These risk alleles are enriched in myeloid cell enhancers suggesting that microglia, the brain-resident macrophages, contribute to AD risk. We have previously identified SPI1/PU.1, a master regulator of myeloid cell development in the brain and periphery, as a genetic risk factor for AD. Higher expression of SPI1 is associated with increased risk for AD, while lower expression is protective. To investigate the molecular and cellular phenotypes associated with higher and lower expression of PU.1 in microglia, we used stable overexpression and knock-down of PU.1 in BV2, an immortalized mouse microglial cell line. Transcriptome analysis suggests that reduced PU.1 expression suppresses expression of homeostatic genes similar to the disease-associated microglia response to amyloid plaques in mouse models of AD. Moreover, PU.1 knock-down resulted in activation of protein translation, antioxidant action and cholesterol/lipid metabolism pathways with a concomitant decrease of pro-inflammatory gene expression. PU.1 overexpression upregulated and knock-down downregulated phagocytic uptake in BV2 cells independent of the nature of the engulfed material. However, cells with reduced PU.1 expression retained their ability to internalize myelin similar to control albeit with a delay, which aligns with their anti-inflammatory profile. Here we identified several microglial responses that are modulated by PU.1 expression levels and propose that risk association of PU.1 to AD is driven by increased pro-inflammatory response due to increased viability of cells under cytotoxic conditions. In contrast, low expression of PU.1 leads to increased cell death under cytotoxic conditions accompanied by reduced pro-inflammatory signaling that decreased A1 reactive astrocytes signature supporting the protective effect of SPI1 genotype in AD. These findings inform future in vivo validation studies and design of small molecule screens for therapeutic discovery in AD.
2020-12-07 | GSE162526 | GEO