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Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9.

ABSTRACT: Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9.

PROVIDER: PRJNA1008451 | ENA |

REPOSITORIES: ENA

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Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9 [scRNA-seq]

Project description:Ossification of the posterior longitudinal ligament (OPLL) is a progressive ectopic bone formation of ligaments and may lead to severe neurological symptoms. However, in addition to conservative therapy for neurological symptoms or surgical management, effective pharmacotherapy and preventive intervention for OPLL remains absent. Here, to reveal the potential therapeutic target we generate single-cell maps of T-OPLL patients. We found that type I IFN signaling pathway is significantly activated during the progression of ossification. Further, stimulation of IFN β obviously promoted the calcium deposition of murine MC3T3-E1 preosteoblasts. We profiled the transcriptome in MC3T3-E1 cells after osteogenic induction, and found that IFN β promoted the expression of Sox9 and SPP1. STAT1 positively regulated the expression of Sox9 and phosphorylated STAT1 occupied on the promoter of Sox9. We also observed the localization of Sox9 in the ossificated region of ligament from OPLL patients. Thus, Sox9 is a target gene of type I IFN pathway during osteogenic induction. Furthermore, blockage of IFNAR1 by anti-IFNAR1 neutralizing antibody significantly impeded osteoblast differentiation induced by IFN β and display efficacy against ossification. Together, these results demonstrated that type I IFN signaling pathway promotes osteoblast differentiation. Anti-IFNAR1 neutralizing antibody could be used as a potential therapy for OPLL by blocking type I IFN signaling pathway.

2023-11-30 | GSE241505 | GEO

Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9 [RNA-seq]

2023-11-30 | GSE241506 | GEO

Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9 [scRNA-seq]

Project description:Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9 [scRNA-seq]

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Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9 [RNA-seq]

Project description:Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9 [RNA-seq]

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Type I IFN signaling pathway promotes osteoblast differentiation through targeting Sox9.

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

2023-11-30 | GSE241507 | GEO

SOX9 Drives WNT Pathway Activation in Prostate Cancer

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SOX9 ameliorates nonalcoholic steatohepatitis through activating AMPK pathway

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Embryonic mouse mammary progenitor cells +/-Sox9

Project description:CRISPR/Cas9-mediated gene targeting of Sox9 from embryonic mammary progenitors cell line eMPC1. Part of a study to assess the effect of Sox9 ablation on embryonic mammary progenitor cell fate and function.

2018-11-30 | E-MTAB-6846 | biostudies-arrayexpress

Sox9-Meis1 inactivation is required for adipogenesis, advancing Pref-1+ to PDGFRa+ cells [microrarray]

Project description:Adipocytes arise from commitment and differentiation of adipose precursors in white adipose tissue (WAT). In studying adipogenesis, precursor markers, including Pref-1 and PDGFRα, are used to isolate precursors from stromal vascular fraction of WAT, but the relationship among the markers is not known. Here, we used Pref-1 promoter-rtTA system in mice for labeling Pref-1+ cells and for inducible inactivation of Pref-1 target, Sox9. We show requirement of Sox9 for maintenance of Pref-1+ proliferative, early precursors. Upon Sox9 inactivation, these Pref-1+ cells become PDGFRa+ cells that express early adipogenic markers. Thus, we show for the first time that Pref-1+ cells precede PDGFRa+ cells in the adipogenic pathway and that Sox9 inactivation is required for WAT growth and expansion. Furthermore, we show that, in maintaining early adipose precursors, Sox9 activates Meis1 which prevents adipogenic differentiation. Our study also demonstrates the Pref-1 promoter-rtTA system for inducible gene inactivation in early adipose precursor population. Sox9 ablation increases PDGFRα+ cells, inhibiting cell cycle, muscle and osteoblast/osteoclast differentiation, while inducing genes of hematopoietic cell lineage and inflammatory response.

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Targeting Hedgehog pathway by Smoothened Antagonist

Project description:Targeting Hedgehog pathway by Smoothened Antagonist

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