Project description:Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions [CEBPbetaKO]

| PRJNA509277 | ENA

Transcription factor C/EBPβ orchestrates DC maturation and functionality under homeostatic and malignant conditions

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

2020-10-20 | GSE123593 | GEO

in vitro DC models

Project description:Global transcriptional analysis was used in order to understand functionality and applicability of in vitro DC models.

2013-03-15 | E-MEXP-3787 | biostudies-arrayexpress

Genome-wide C/EBPβ traget genes in C/EBPβ-overexpressed HL-60 cells.

Project description:To characterize genome-wide C/EBPβ traget genes in C/EBPβ-overexpressed HL-60 cells by ChIP-seq.

2018-06-13 | GSE100486 | GEO

Identification of PRDM15 Cistrome in Emu-Myc Lymphoma cells

Project description:Genome-wide binding targets of PRDM15 were identified in Emu-Myc Lymphomas

2019-07-04 | GSE116905 | GEO

C/EBPβ deficiency reshapes microglial gene expression

Project description:CCAAT/enhancer binding protein β (C/EBPβ) is a transcription factor that regulates the expression of important pro-inflammatory genes in microglia. Mice deficient for C/EBPβ show protection against excitotoxic and ischemic CNS damage but the involvement of the various C/EBPβ expressing cell types in this neuroprotective effect is not solved. Since C/EBPβ-deficient microglia show attenuated neurotoxicity in culture we hypothesized that specific C/EBPβ deficiency in microglia could be neuroprotective in vivo. In this study we have tested this hypothesis by generating mice with myeloid C/EBPβ deficiency. Mice with myeloid C/EBPβ deficiency were generated by crossing LysMCre and C/EBPβfl/fl mice . Primary microglial cultures from C/EBPβfl/fl (named here as WT) and LysMCre-C/EBPβfl/fl (named here as KO) mice were treated with lipopolysaccharide ± interferon γ (IFNγ) for 6 h and gene expression was analyzed by RNA sequencing. LysMCre-C/EBPβfl/fl mice showed an efficiency of C/EBPβ deletion of 100% in cultured microglia. Transcriptomic analysis of C/EBPβ-deficient primary microglia revealed C/EBPβ-dependent expression of 1068 genes, significantly enriched in inflammatory and innate immune responses GO terms. This study provides new data that support a central role for C/EBPβ in the biology of activated microglia.

2017-06-13 | GSE90046 | GEO

The transcription factor C/EBPβ orchestrates dendritic cell maturation and functionality under homeostatic and malignant conditions.

Project description:Dendritic cell (DC) maturation is a prerequisite for the induction of adaptive immune responses against pathogens and cancer. Transcription factor (TF) networks control differential aspects of early DC progenitor versus late-stage DC cell fate decisions. Here, we identified the TF C/EBPβ as a key regulator for DC maturation and immunogenic functionality under homeostatic and lymphoma-transformed conditions. Upon cell-specific deletion of C/EBPβ in CD11c+MHCIIhi DCs, gene expression profiles of splenic C/EBPβ-/- DCs showed a down-regulation of E2F cell cycle target genes and associated proliferation signaling pathways, whereas maturation signatures were enriched. Total splenic DC cell numbers were modestly increased but differentiation into cDC1 and cDC2 subsets were unaltered. The splenic CD11c+MHCIIhiCD64+ DC compartment was also increased, suggesting that C/EBPβ deficiency favors the expansion of monocytic-derived DCs. Expression of C/EBPβ could be mimicked in LAP/LAP* isoform knockin DCs, whereas the short isoform LIP supported a differentiation program similar to deletion of the full-length TF. In accordance with E2F1 being a negative regulator of DC maturation, C/EBPβ-/- bone marrow-derived DCs matured much faster enabling them to activate and polarize T cells stronger. In contrast to a homeostatic condition, lymphoma-exposed DCs exhibited an up-regulation of the E2F transcriptional pathways and an impaired maturation. Pharmacological blockade of C/EBPβ/mTOR signaling in human DCs abrogated their protumorigenic function in primary B cell lymphoma cocultures. Thus, C/EBPβ plays a unique role in DC maturation and immunostimulatory functionality and emerges as a key factor of the tumor microenvironment that promotes lymphomagenesis.

| S-EPMC7584915 | biostudies-literature

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