TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [RNA-seq]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA721180 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14207978.fastq.gz | Fastqsanger.gz | |||
| SRR14207979.fastq.gz | Fastqsanger.gz | |||
| SRR14207980.fastq.gz | Fastqsanger.gz | |||
| SRR14207981.fastq.gz | Fastqsanger.gz | |||
| SRR14207982.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 18 |
Similar Datasets
Project description:TNF plays a key role in inflammation and bone resorption. However, the mechanisms regulating TNF-mediated osteoclastogenesis remain largely unclear because its direct osteoclastogenic ability is weak. Here, we found that TGFβ priming enables TNF to effectively induce osteoclastogenesis from macrophages, independently of the osteoclastogenic action of RANKL. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not physiological, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms macrophage response to TNF towards osteoclastogenesis by remodeling chromatin accessibility and histone modification. TGFβ and TNF induce an unconventional osteoclastogenic program, which includes the suppression of the TNF-induced IRF1-IFNβ-IFN stimulated gene (ISG) axis, promotion of IRF8 degradation and B-Myb induction. These mechanisms are present in RA, in which TGFβ level is elevated and correlated with osteoclast activity. Our findings identify a function and mechanism of action for TGFβ in TNF-mediated inflammatory osteoclastogenesis, and open avenues for selective treatment of inflammatory bone loss.
2022-03-24 | GSE171841 | GEO
Project description:TNF plays a key role in inflammation and bone resorption. However, the mechanisms regulating TNF-mediated osteoclastogenesis remain largely unclear because its direct osteoclastogenic ability is weak. Here, we found that TGFβ priming enables TNF to effectively induce osteoclastogenesis from macrophages, independently of the osteoclastogenic action of RANKL. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not physiological, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms macrophage response to TNF towards osteoclastogenesis by remodeling chromatin accessibility and histone modification. TGFβ and TNF induce an unconventional osteoclastogenic program, which includes the suppression of the TNF-induced IRF1-IFNβ-IFN stimulated gene (ISG) axis, promotion of IRF8 degradation and B-Myb induction. These mechanisms are present in RA, in which TGFβ level is elevated and correlated with osteoclast activity. Our findings identify a function and mechanism of action for TGFβ in TNF-mediated inflammatory osteoclastogenesis, and open avenues for selective treatment of inflammatory bone loss.
2022-03-24 | GSE171839 | GEO
Project description:TNF plays a key role in inflammation and bone resorption. However, the mechanisms regulating TNF-mediated osteoclastogenesis remain largely unclear because its direct osteoclastogenic ability is weak. Here, we found that TGFβ priming enables TNF to effectively induce osteoclastogenesis from macrophages, independently of the osteoclastogenic action of RANKL. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not physiological, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms macrophage response to TNF towards osteoclastogenesis by remodeling chromatin accessibility and histone modification. TGFβ and TNF induce an unconventional osteoclastogenic program, which includes the suppression of the TNF-induced IRF1-IFNβ-IFN stimulated gene (ISG) axis, promotion of IRF8 degradation and B-Myb induction. These mechanisms are present in RA, in which TGFβ level is elevated and correlated with osteoclast activity. Our findings identify a function and mechanism of action for TGFβ in TNF-mediated inflammatory osteoclastogenesis, and open avenues for selective treatment of inflammatory bone loss.
2022-03-24 | GSE171842 | GEO
Project description:TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis
| PRJNA721177 | ENA
Project description:TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [ATAC-seq]
| PRJNA721181 | ENA
Project description:TGFβ reprograms TNF stimulation of macrophages towards osteoclastogenesis [CUT&RUN]
| PRJNA721182 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-03-22 | GSE171843 | GEO
Project description:It is well-established that receptor activator of NF-κB ligand (RANKL) is the inducer of physiological osteoclast differentiation. However, the specific drivers and mechanisms driving inflammatory osteoclast differentiation under pathological conditions remain obscure. This is especially true given that inflammatory cytokines such as tumor necrosis factor (TNF) demonstrate little to no ability to directly drive osteoclast differentiation. Here, we found that transforming growth factor β (TGFβ) priming enables TNF to effectively induce osteoclastogenesis, independently of the canonical RANKL pathway. Lack of TGFβ signaling in macrophages suppresses inflammatory, but not basal, osteoclastogenesis and bone resorption in vivo. Mechanistically, TGFβ priming reprograms the macrophage response to TNF by remodeling chromatin accessibility and histone modifications, and enables TNF to induce a previously unrecognized non-canonical osteoclastogenic program, which includes suppression of the TNF-induced IRF1-IFNβ-IFN-stimulated-gene axis, IRF8 degradation and B-Myb induction. These mechanisms are active in rheumatoid arthritis, in which TGFβ level is elevated and correlates with osteoclast activity. Our findings identify a TGFβ/TNF-driven inflammatory osteoclastogenic program, and may lead to development of selective treatments for inflammatory osteolysis.
| S-EPMC9263175 | biostudies-literature
Project description:Glioblastoma stem cells (GSCs) fate is controlled by environmental cues, among which cytokines play a crucial role. The transforming growth factor β (TGFβ) family signaling pathways controls GSCs. On one hand, TGFβ promotes cell proliferation in GBM, it induces the expression of platelet-derived growth factor-B (PDGFB). Moreover, TGFβ, via its signaling mediators Smad2/3, induces the expression of the cytokine leukemia inhibitory factor (LIF) and Sox4, which in turn enhances the expression of the stem cell transcription factor Sox2; this increases the self-renewal capacity of the GSCs and their stemness characteristics, and enhances the GSC tumor-initiating potential. On the other hand, Bone morphogenic proteins (BMPs) are known to promote GSC differentiation towards the astrocytic phenotype. To further understand which genes are regulated by TGFβ and BMP7 in GSCs we performed a microarray in the Affymetrix HTA2 platform in three different glioblastoma cell line, U2987, and two patient-derived glioblastoma stem cells, U3031MG and U3034MG, in the presence or absence of 5 ng/ml of TGFβ or 30 ng/ml BMP7 for 24 h, three biological replicates per condition.
2020-09-01 | E-MTAB-9076 | biostudies-arrayexpress
Project description:Clarification of the mechanisms underlying osteoclast differentiation enable us to understand the physiology of bone metabolism as well as the pathophysiology of bone diseases, such as osteoporosis. Recently, it has been reported that epigenetics can determine the cell fate and regulate cell type specific gene expression. However, little is known about epigenetics during osteoclastogenesis. To reveal a part of epigenetics, especially focused on chromatin dynamics, during early osteoclastogenesis and identify novel transcription factors involved in osteoclastogenesis, we investigated genome-wide analysis of open chromatin during receptor activator of nuclear factor-M-NM-:B ligand (RANKL)-induced osteoclastogenesis using DNase I hypersensitive sites sequencing (DNase-seq). DNase-seq was performed using the extracted nuclei obtained from RAW264 cells treated with or without RANKL for 24 hours, followed by several bioinformatic analyses. DNase I hypersensitive sites (DHSs) during RANKL-induced osteoclastogenesis were dynamically changed and accumulated in promoter regions, although the distributions of DHSs among cis-regulatory DNA regions were identical regardless of RANKL stimulation. Motif discoveries from DHSs successfully identified well-known osteoclastogenic transcription factors such as Jun, CREB1, FOS, ATF2 and ATF4, but also novel transcription factors for osteoclastogenesis such as Zscan10, Atf1 Nrf1 and Srebf2. siRNA knockdown of these identified novel transcription factors impaired osteoclastogenesis. Taken together, DNase-seq can be a useful tool for comprehension of epigenetics, especially chromatin dynamics during osteoclastogenesis and for identification of novel transcription factors involved in osteoclastogenesis. This study may reveal underlying mechanisms that determine cell-type specific differentiation of bone cells and may lead to investigate novel therapeutic targets for osteoporosis. Examination of genome-wide DNase Hypersensitive Sites in differentiated and undifferentiated RAW264 cells.
2014-11-05 | E-GEOD-54139 | biostudies-arrayexpress