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Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE151483 | GEO | 2020/09/11

REPOSITORIES: GEO

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Monocyte Subsets With High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8.

Project description:Osteoclasts (OCs) are bone-resorbing cells formed by the serial fusion of monocytes. In mice and humans, three distinct subsets of monocytes exist; however, it is unclear if all of them exhibit osteoclastogenic potential. Here we show that in wild-type (WT) mice, Ly6Chi and Ly6Cint monocytes are the primary source of OC formation when compared to Ly6C- monocytes. Their osteoclastogenic potential is dictated by increased expression of signaling receptors and activation of preestablished transcripts, as well as de novo gain in enhancer activity and promoter changes. In the absence of interferon regulatory factor 8 (IRF8), a transcription factor important for myelopoiesis and osteoclastogenesis, all three monocyte subsets are programmed to display higher osteoclastogenic potential. Enhanced NFATc1 nuclear translocation and amplified transcriptomic and epigenetic changes initiated at early developmental stages direct the increased osteoclastogenesis in Irf8-deficient mice. Collectively, our study provides novel insights into the transcription factors and active cis-regulatory elements that regulate OC differentiation. © 2020 American Society for Bone and Mineral Research (ASBMR).

| S-EPMC8168257 | biostudies-literature

Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [RNA-Seq]

Project description:Currently, it is unclear if all monocyte subsets exhibit osteoclastogenic potential. Furthermore, the role of lineage determining TFs in regulating OC differentiation on a genome-wide scale remains poorly understood. In this study, we utilized a novel Irf8 conditional knockout (Irf8 cKO) mouse model to characterize the importance of IRF8 in OC progenitor development and epigenetic regulation of OC differentiation. We performed RNA-seq on Irf8 gWT, gKO, cWT and cKO BMMs, preosteoclasts (PreOCs), and OCs. Cells were analyzed prior to (BMMs) and 3 days (PreOCs) and 6 days (OCs) after RANKL stimulation. Here we show that greater a number of genes are significantly upregulated in Irf8 cKO OCs when compared to WT and Irf8 gKO OCs. Altogether, our data shows that Irf8 cKO mice provide more precise/reliable OC-specific transcriptomic results when compared to Irf8 gKO mice.

2020-09-11 | GSE151388 | GEO

Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [ChIP-Seq]

Project description:Currently, the epigenetic mechanisms governing the osteoclast differentiation process remains poorly understood. To investigate the combinatorial activity of TFs, cis-regulatory elements, and the enhancer landscape that establish and maintain osteoclast transcriptional identity, we profiled histone modifications (H3K4me1, H3K4me3, H3K27ac, H3K27me3) and PU.1 and IRF8 binding by ChIP-seq. RNA-seq data from sorted Ly6Chi, Ly6Cint, and Ly6C– cells were overlaid with ChIP-seq data to identify epigenetic changes specific to each subset and genotype. Our data suggest that the Ly6Chi inflammatory monocytes and Ly6Cint cells are transcriptionally and epigenetically programmed to differentiate in mature osteoclasts when compared to Ly6C– anti-inflammatory monocytes. A combinatorial activity of TFs and cis-regulatory elements in the vicinity of several osteoclast-specific genes are responsible for establishing and maintaining osteoclast identity in these subsets. In Irf8 cKO mice, several promoters and enhancers established during the progenitor stage may be critical for initiating early lineage commitment and priming monocyte subsets to differentiate into robust osteoclasts.

2020-09-19 | GSE151481 | GEO

Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [RNA-Seq sorted cells]

Project description:Currently, it is unclear if all monocyte subsets exhibit osteoclastogenic potential. Furthermore, the role of lineage determining TFs in regulating OC differentiation on a genome-wide scale remains poorly understood. In this study, we utilized a novel Irf8 conditional knockout (Irf8 cKO) mouse model to characterize the importance of IRF8 in OC progenitor development and epigenetic regulation of OC differentiation. To identify global transcriptional program governing the osteoclastogenic potential of Ly6Chi, Ly6Cint, and Ly6C– monocytes, and how it may be further influenced by IRF8 deficiency, we performed RNA-seq on sorted Ly6Chi, Ly6Cint, and Ly6C– cells from WT and Irf8 cKO mice. Cells were analyzed prior to (BMMs) and 4 days after RANKL stimulation (OCs). Here we show that WT Ly6Chi and Ly6Cint monocytes developmentally contain OC-specific transcripts, which are augmented upon RANKL stimulation. Additionally, in the absence of IRF8, OC-specific transcripts in all three monocyte subsets are primed to robustly respond to RANKL stimulation.

2020-09-11 | GSE151480 | GEO

Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8

Project description:Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8

| PRJNA635933 | ENA

Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [ChIP-Seq]

Project description:Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [ChIP-Seq]

| PRJNA635936 | ENA

Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [RNA-Seq]

Project description:Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [RNA-Seq]

| PRJNA635657 | ENA

Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [RNA-Seq sorted cells]

Project description:Monocyte Subsets with High Osteoclastogenic Potential and Their Epigenetic Regulation Orchestrated by IRF8 [RNA-Seq sorted cells]

| PRJNA635935 | ENA

IRF8-induced monocyte differentiation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-01-24 | E-GEOD-38825 | biostudies-arrayexpress

IRF8-induced monocyte differentiation

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

2013-01-24 | GSE38825 | GEO