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Integrative Single-Cell RNA-Seq and ATAC-Seq Identifies Transcriptional and Epigenetic Blueprint Guiding Osteoclastogenic Trajectory [scATAC-seq]

ABSTRACT: Osteoclasts (OCs) are multinucleated bone resorbing cells essential for skeletal development and remodeling. In adulthood, OCs originate from the serial fusion of monocytes, yet the transcriptional and epigenetic mechanisms shaping their osteoclastogenic potential at a single cell resolution remain poorly understood. Here, we employed an integrative multi-omics approach, combining single-cell (sc) RNA-seq, scATAC-seq, bulk RNA-seq, and ChIP-seq, to comprehensively define the regulatory landscape of osteoclastogenesis in wild-type (WT) and Irf8 conditional knockout (cKO) mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE288654 | GEO | 2025/10/01

REPOSITORIES: GEO

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Integrative Single-Cell RNA-Seq and ATAC-Seq Identifies Transcriptional and Epigenetic Blueprint Guiding Osteoclastogenic Trajectory [scRNA-seq]

Project description:Osteoclasts (OCs) are multinucleated bone resorbing cells essential for skeletal development and remodeling. In adulthood, OCs originate from the serial fusion of monocytes, yet the transcriptional and epigenetic mechanisms shaping their osteoclastogenic potential at a single cell resolution remain poorly understood. Here, we employed an integrative multi-omics approach, combining single-cell (sc) RNA-seq, scATAC-seq, bulk RNA-seq, and ChIP-seq, to comprehensively define the regulatory landscape of osteoclastogenesis in wild-type (WT) and Irf8 conditional knockout (cKO) mice.

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Integrative Single-Cell RNA-Seq and ATAC-Seq Identifies Transcriptional and Epigenetic Blueprint Guiding Osteoclastogenic Trajectory [scATAC-seq]

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Integrative Single-Cell RNA-Seq and ATAC-Seq Identifies Transcriptional and Epigenetic Blueprint Guiding Osteoclastogenic Trajectory [scRNA-seq]

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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.

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Human FcγRIIa mediates osteoclastogenesis through a novel noncanonical pathway independent of RANKL and inflammatory cytokines

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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.

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Transcriptional profiles of genes in the early stage of osteoclastogenesis

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Project description:Effect of c-fos expression in osteoclastogenic splenocytes.

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