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RNAseq analysis of resting and TDM-stimulated DGCR8-deficient macrophages

ABSTRACT: RNAseq analysis of resting and TDM-stimulated DGCR8-deficient macrophages

PROVIDER: PRJNA628689 | ENA |

REPOSITORIES: ENA

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RNAseq analysis of resting and TDM-stimulated DGCR8-deficient macrophages

Project description:Pathogenic mycobacteria subvert immune responses to survive and replicate in macrophages. Mycobacterial cell wall components are sensed by several C-type lectin receptors, including MINCLE, the receptor for the cord factor trehalose-6,6-dimycolate (TDM). Regulation of innate immune cells relies on miRNAs, some of which are induced by mycobacterial ligands. Thus, MTB may exploit host miRNAs to establish its niche in macrophages. Here, we have employed conditional knockout mice for the microprocessor component DGCR8 to investigate the impact of miRNAs on the macrophage response to the mycobacterial cord factor. Deletion of DGCR8 during differentiation of macrophages from bone marrow progenitors significantly reduced the cell yield, but did not interfere with macrophage differentiation as determined by typical surface marker expression and phagocytic capacity. DGCR8-deficient macrophages expressed reduced levels of constitutive and TDM-inducible miRNAs, yet in turn accumulated primary miRNA transcripts. RNAseq revealed a modest type I interferon (IFN) signature in resting DGCR8-deficient macrophages. Stimulation of DGCR8-deficient macrophages with TDM induced overshooting and prolonged expression of interferon response genes, which was associated with enhanced expression of IFNb and could be largely prevented by antibodies to type I interferon. In turn, exogenous IFNb upregulated CXCL10 and CD69 to similar levels in control and DGCR8-deficient macrophages, indicating that signaling downstream of the type I IFN receptor was unaltered. Infection with live Mycobacterium bovis Bacille Calmette-Guerin (BCG) replicated the enhanced interferon response of DGCR8-deficient macrophages. Together, our results reveal an essential role for DGCR8 in curbing IFNb expression and IFN-dependent macrophage activation by mycobacteria.

2020-04-28 | GSE149441 | GEO

Stabilizing Heterochromatin by DGCR8 Alleviates Senescence and Osteoarthritis

Project description:DiGeorge syndrome critical region 8 (DGCR8) is a critical component of the canonical microprocessor complex for microRNA biogenesis. However, the non-canonical functions of DGCR8 have not been studied. Here, we demonstrate that DGCR8 plays an important role in maintaining heterochromatin organization and attenuating aging. An N-terminal-truncated version of DGCR8 (DR8dex2) accelerated senescence in human mesenchymal stem cells (hMSCs) independent of its miRNA-processing activity, which is mediated by its C-terminal domains. Further studies revealed that DGCR8 maintained heterochromatin organization by interacting with the nuclear envelope protein Lamin B1, and heterochromatin-associated proteins, KAP1 and HP1 Overexpression of any of these proteins, including DGCR8, reversed premature senescent phenotypes in DR8dex2 hMSCs. Finally, DGCR8 was downregulated in pathologically and naturally aged hMSCs, whereas DGCR8 overexpression alleviated hMSC aging and osteoarthritis in mice. Taken together, these analyses uncovered a novel, miRNA processing-independent role for DGCR8 in maintaining heterochromatin organization and attenuating senescence. DGCR8 may therefore represent a new therapeutic target for alleviating human aging-related disorders.

2019-05-28 | PXD013856 | Pride

Gene expression variation in horse placental and fetal tissue, and resting and stimulated horse lymphocytes

Project description:This SuperSeries is composed of the following subset Series: GSE35741: Gene expression variation in horse placental and fetal tissue, and resting and stimulated horse lymphocytes [Agilent-018932] GSE35742: Gene expression variation in horse placental tissue, and resting and stimulated horse lymphocytes [Agilent-021322] Refer to individual Series

2012-02-14 | E-GEOD-35743 | biostudies-arrayexpress

Microarray screening of differentially expressed lncRNAs between resting and IL-4 stimulated microglia

Project description:To find potential lncRNAs participating in the regulation of microglial polarization, we employed microarray screening to find differentially expressed lncRNAs between resting and IL-4 stimulated primary cultured microglia

2017-05-24 | GSE99216 | GEO

Single cell five-prime end sequencing of PBMC - resting and stimulated

Project description:Single cell five-prime end sequencing of PBMC - resting and stimulated. Used to asses the five-prime sequencing method in the detection of cis-regulatory elements using SCAFE (see publication)

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scRNAseq analysis comparing primary CD4+ T cells in resting memory state or stimulated with anti-CD3/anti-CD28 states and the effect of loss of ADAP1

Project description:By comparing the differenital gene expression of resting memory CD4+ cell and their transition to stimulated states, we are able to interrogate the effects that loss of ADAP1 has on T cell activation. Comparison between DEG of Ctrl cells (resting to stimulated) vs ADAP1 CRISPR cells (resting to stimulated) yielded 515 overlapping DEG (397 upregulated and 118 downregulated). Out of which, 364 of the 397 overlapping upregulated genes induced to significantly lower levels in ADAP1CRISPR cells compared to the level of fold change induction in Ctrl cells.

2022-01-27 | GSE169339 | GEO

Single cell five-prime end sequencing of PBMC - resting and stimulated

Project description:Single cell five-prime end sequencing of PBMC - resting and stimulated

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Gene expression variation in horse placental tissue, and resting and stimulated horse lymphocytes [Agilent-021322]

Project description:We undertook gene expression microarray experiments to identify genes that are differentially expressed in invasive (Chorionic Girdle) and non-invasive (Chorion) placental tissue, and resting and Pokeweed Mitogen (PWM) stimulated horse lymphocytes. Conceptus tissues were dissected to obtain chorionic girdle, and chorion. Freshly isolated horse peripheral blood lymphocytes were split and harvested immediately, or stimulated with PWM and harvested over a five day period. These experiments utilized a commercially available Agilent horse array that featured >43,000 probes on a 4x44k array format. Three day 33-35 chorionic girdle RNAs were compared to matching chorion RNAs. Gene expression in resting lymphocytes was compared to gene expression in PWM treated lymphocytes.

2012-02-14 | E-GEOD-35742 | biostudies-arrayexpress

Single cell ATAC-seq of human peripheral blood mononuclear cells under resting and stimulated conditions

Project description:Single cell ATAC-seq of PBMC - resting and stimulated. Used for comparison to asses the capabilies of the five-prime sequencing method in the detection of cis-regulatory elements using SCAFE (see publication).

2021-04-13 | E-MTAB-10382 | biostudies-arrayexpress

Transcription profiling of human resting and zymosan A-stimulated monocyte-derived macrophages in the absence or presence of PMN-Ectosomes

Project description:In order to define the inhibitory activity of PMN-Ectosomes, we investigated the early gene expression profiles of resting and zymosan A-stimulated human monocyte-derived macrophages in the absence or presence of PMN-Ectosomes. Experiment Overall Design: We cultured monocytes isolated from fresh buffy coats of 4 healthy donors (2 males and 2 females between the ages of 20 to 45) for 7 days at 37Â°C. At day 7, macrophages were cultured for another 3 hours alone, in presence of PMN-Ectosomes, with zymosan A, and with zymosan A and PMN-Ectosomes.

2009-01-25 | E-GEOD-14419 | biostudies-arrayexpress

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