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Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4

ABSTRACT: Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4

PROVIDER: PRJNA430266 | ENA |

REPOSITORIES: ENA

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Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4

Project description:Obesity, a prevalent condition in adults and children, impairs bone marrow (BM) function. However, the underlying mechanisms are unclear. Here we show that obese mice exhibit poor emergency immune responses in a toll-like receptor 4 (TLR4)-dependent manner. Canonical myeloid genes (Csf1r, Spi1, Runx1) are enhanced, and lymphoid genes (Flt3, Tcf3, Ebf1) are reduced. Using adoptive transfer and mixed BM chimera approaches we demonstrate that myeloid>lymphoid bias arises after six weeks of high fat diet and depends on precursor cell-autonomous TLR4. Further, lean mice exposed to the TLR4 ligand lipopolysaccharide (LPS) at doses similar to that detectable in obese serum recapitulates BM lympho-myeloid alterations. Together, these results establish a mechanistic contribution of BM cell-intrinsic TLR4 to obesity-driven BM malfunction and demonstrate the importance of LPS. Our findings raises important questions about the impact of maternal obesity and endotoxemia to fetal hematopoiesis, as fetal immune precursors are also sensitive to TLR4 signals.

2018-01-17 | GSE109269 | GEO

Bone marrow lympho-myeloid malfunction in obesity requires precursor cell-autonomous TLR4.

Project description: Not available

| S-EPMC5816016 | biostudies-literature

Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8

Project description:Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8

| PRJNA479472 | ENA

Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8 [ChIP-seq]

Project description:Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8 [ChIP-seq]

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Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8 [RNA-seq]

Project description:Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8 [RNA-seq]

| PRJNA479476 | ENA

Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8 [ATAC-seq]

Project description:Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8 [ATAC-seq]

| PRJNA479474 | ENA

Induction of autonomous memory alveolar macrophages requires T-cell help and is critical to trained immunity

Project description:Induction of autonomous memory alveolar macrophages requires T-cell help and is critical to trained immunity

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RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling

Project description:The toll-like receptor 4 (TLR4) is a central regulator of innate immune signaling that primarily recognizes bacterial lipopolysaccharide (LPS) cell wall constituents to trigger cytokine secretion. We identify the intramembrane protease RHBDL4 as a negative regulator of TLR4 signaling. We show that RHBDL4-triggers the degradation of TLR4’s trafficking factor TMED7, a member of the p24 family of COPII adaptor proteins, which counteracts the transport of TLR4 to the cell surface. Besides TMED7, RHBDL4 cleaves a subset of related p24 cargo receptors, suggesting that this is a general protein abundance control mechanism to regulate the loading of specific secretory proteins into COPII vesicles. Notably, TLR4 activation by LPS mediates transcriptional upregulation of RHBDL4. Hence, TLR4 activation triggers an RHBDL4-dependent negative feedback loop to reduce the export of newly synthesized TLR4 molecules from the endoplasmic reticulum into COPII-coated vesicles. This secretory cargo tuning mechanism prevents the over-activation of TLR4-dependent signaling and consequently alleviates septic shock in a mouse model.

2024-01-09 | PXD045934 | Pride

Oligodendrocyte precursor differentiation and survival requires chromatin remodeling by Chd7 and Chd8 [ATAC-seq]

Project description:Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming implicating chromatin remodeling. Here, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin-binding profile combined with transcriptome and open-chromatin analysis of Chd7-deleted OPCs, demonstrates that Chd7 controls OPC differentiation through chromatin-opening and transcriptional activation of key regulators such as Sox10, Nkx2.2 and Gpr17. Chd7 is however dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by its chromatin binding profile. Furthermore, Chd7 protects non-proliferative OPCs from apoptosis by chromatin-closing and transcriptional repression of p53. Mutations in CHD7 and CHD8 are associated with developmental disorders, such as CHARGE syndrome and autism respectively, and our results offer new avenues to understand and modulate their functions in disease.

2018-08-29 | GSE116598 | GEO

Expression data from Caco-2 cells expressing TLR4 and associated mutants

Project description:Common missense mutations (D299G, T399I) have been recently identified in the human TLR4 gene. The aim of this study was to determine how TLR4 and associated mutants affect gene expression in Caco-2 cells. We used microarrays to asses gene expression profiles in Caco-2 stably overexpressing TLR4-WT, TLR4-D299G, TLR4-T399I or untransfected. Caco-2 clones stably overexpressing HA-tagged wildtype TLR4-WT, mutant TLR4-D299G or TLR4-T399I were generated. Prior to analysis, cell clones were cultured for 8 days in all experiments. RNA (triplicate) was extracted and hybridized on Affymetrix microarrays.

2011-10-10 | E-GEOD-26226 | biostudies-arrayexpress

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