Transcriptomic Analysis Reveals TME-Mediated Macrophage IFIT1 Upregulation and CX3CR1 Suppression Drive Osteosarcoma Progression
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PROVIDER: PRJNA1306604 | ENA |
REPOSITORIES: ENA
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Project description:Osteosarcoma (OS) is one of the most common bone tumors which prognosis of patients is unsatisfactory. Due to the stagnancy in conventional treatments, researchers begin to find therapeutic targets from tumor microenvironment (TME) and tumor associated macrophages (TAM). We aim to investigate the influence of the effects of OS TME on gene expression of macrophages which may provide reference to OS treatment. RNA sequencing was performed on BMMs cultured with or without K7M2 CM for 48 hours to analyze gene expression changes.
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Project description:The aging brain shows changes in microglial function, morphology, and phenotype, indicating chronic microglial activation. CX3CR1 is crucial for microglial chemotaxis, phagocytosis, and activation. However, its exact role in the aging brain is not well understood. In this study, we examined the expression of CX3CR1 in the brains of middle-aged mice (10 months old) and explored its functional implications by conducting proteomic profiling in CX3CR1-deficient mouse cerebrum. Proteomic analysis revealed an enrichment of differentially expressed proteins (DE-proteins) in the cerebrum of middle-aged mice in GO pathways such as “synapse”, “translation”, and “ribosome”. CX3CR1 deficiency affected protein levels in GO pathways such as “glutamatergic synapse” and “RNA splicing.” We also detected the proteomics in age-matched 5xFAD mice for comparison, since this mouse strain featured aberrant microglial activation and CX3CR1 upregulation in the hippocampus and frontal cortex. Our findings demonstrated that CX3CR1 was upregulated to maintain synaptic homeostasis probably through regulating microglial activation and phagocytosis in the brains of middle-aged mice. CX3CR1 may represent a promising therapeutic target for alleviating the effects of aging and preventing neurodegeneration.
2025-07-05 | PXD058961 | Pride
Project description:WWOX promotes osteosarcoma development via upregulation of Myc [RNA-Seq]
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Project description:WWOX promotes osteosarcoma development via upregulation of Myc [ChIP-Seq]
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Project description:Early transplantation of mesenchymal stem cells (MSCs) showed promise in rescuing cardiac function and alleviating ventricular remodeling post-myocardial infarction (MI) while regulatory T cells (Treg) either. However, the crosstalk between them remains fully elusive. To explore mechanisms optimizing MSC therapy from Treg immunoregulatory and develop potential therapeutic targets, adipose-derived stem cells (ADSCs), an easily accessible MSC, were applied. The Treg depletion diminished the cardioprotective effects of ADSCs, causing both systolic dysfunction and cardiac fibrosis. Tregs promoted ADSC retention by proliferation and migration activation with further myogenic differentiation. RNA-sequencing analysis revealed Treg co-culture induced a myogenic differentiation mRNA profile in ADSCs, significantly downregulating Ifit1. IFIT1 downregulation resulted in cardiomyocyte-like differentiation in ADSCs, evidenced by increased myogenic markers and spontaneous beating. Mechanistically, IFIT1 knockdown provoked upregulation of E2F1 protein without altering E2f1 mRNA levels. IFIT1 specifically bound to E2f1 mRNA to inhibit translation, reducing polysomes while knockdown introduced myogenic translational profile. The rAAV9-sh-Ifit1 injection restored systolic dysfunction, reduced fibrosis, and attenuated cardiac hypertrophy. This study uncovered a novel mechanism whereas Tregs potentiated the therapeutic efficacy of ADSCs in MI by downregulating IFIT1, thereby promoting E2f1 translation and myogenic differentiation, offering a potential target to improve cardiac repair strategies.
2024-12-16 | GSE284366 | GEO
Project description:Early transplantation of mesenchymal stem cells (MSCs) showed promise in rescuing cardiac function and alleviating ventricular remodeling post-myocardial infarction (MI) while regulatory T cells (Treg) either. However, the crosstalk between them remains fully elusive. To explore mechanisms optimizing MSC therapy from Treg immunoregulatory and develop potential therapeutic targets, adipose-derived stem cells (ADSCs), an easily accessible MSC, were applied. The Treg depletion diminished the cardioprotective effects of ADSCs, causing both systolic dysfunction and cardiac fibrosis. Tregs promoted ADSC retention by proliferation and migration activation with further myogenic differentiation. RNA-sequencing analysis revealed Treg co-culture induced a myogenic differentiation mRNA profile in ADSCs, significantly downregulating Ifit1. IFIT1 downregulation resulted in cardiomyocyte-like differentiation in ADSCs, evidenced by increased myogenic markers and spontaneous beating. Mechanistically, IFIT1 knockdown provoked upregulation of E2F1 protein without altering E2f1 mRNA levels. IFIT1 specifically bound to E2f1 mRNA to inhibit translation, reducing polysomes while knockdown introduced myogenic translational profile. The rAAV9-sh-Ifit1 injection restored systolic dysfunction, reduced fibrosis, and attenuated cardiac hypertrophy. This study uncovered a novel mechanism whereas Tregs potentiated the therapeutic efficacy of ADSCs in MI by downregulating IFIT1, thereby promoting E2f1 translation and myogenic differentiation, offering a potential target to improve cardiac repair strategies.
2025-01-16 | GSE286274 | GEO
Project description:Early transplantation of mesenchymal stem cells (MSCs) showed promise in rescuing cardiac function and alleviating ventricular remodeling post-myocardial infarction (MI) while regulatory T cells (Treg) either. However, the crosstalk between them remains fully elusive. To explore mechanisms optimizing MSC therapy from Treg immunoregulatory and develop potential therapeutic targets, adipose-derived stem cells (ADSCs), an easily accessible MSC, were applied. The Treg depletion diminished the cardioprotective effects of ADSCs, causing both systolic dysfunction and cardiac fibrosis. Tregs promoted ADSC retention by proliferation and migration activation with further myogenic differentiation. RNA-sequencing analysis revealed Treg co-culture induced a myogenic differentiation mRNA profile in ADSCs, significantly downregulating Ifit1. IFIT1 downregulation resulted in cardiomyocyte-like differentiation in ADSCs, evidenced by increased myogenic markers and spontaneous beating. Mechanistically, IFIT1 knockdown provoked upregulation of E2F1 protein without altering E2f1 mRNA levels. IFIT1 specifically bound to E2f1 mRNA to inhibit translation, reducing polysomes while knockdown introduced myogenic translational profile. The rAAV9-sh-Ifit1 injection restored systolic dysfunction, reduced fibrosis, and attenuated cardiac hypertrophy. This study uncovered a novel mechanism whereas Tregs potentiated the therapeutic efficacy of ADSCs in MI by downregulating IFIT1, thereby promoting E2f1 translation and myogenic differentiation, offering a potential target to improve cardiac repair strategies.
2025-01-16 | GSE286132 | GEO
Project description:The efficacy of immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) treatment remains limited, warranting further investigation into the underlying mechanisms. Accumulating evidence indicates that myeloid cells within the tumor microenvironment (TME) play a role in immune evasion and treatment resistance. In this study, we aimed to explore the contribution of tumor-associated macrophages (TAMs) in the HCC TME. Our findings unveil the critical involvement of CX3C motif chemokine receptor 1 (CX3CR1)-positive TAMs in inducing T cell exhaustion through interleukin-27 (IL-27) secretion, providing valuable insights into the mechanisms underlying the suboptimal efficacy of anti-PD-1 therapy in HCC. Additionally, we identified prostaglandin E2 (PGE2) released by immune-attacked tumor cells as a key driver of CX3CR1+ TAM recruitment. To enhance the therapeutic response to current anti-PD-1 therapy, we propose a novel treatment strategy that combines targeted depletion of CX3CR1+ TAMs with anti-PD-1 therapy. Overall, our study contributes to the understanding of TAMs' role in cancer immunotherapy and presents potential clinical implications for HCC treatment. By targeting CX3CR1+ TAMs in conjunction with anti-PD-1 therapy, we have the potential to enhance the effectiveness of immunotherapeutic interventions in HCC patients.
2024-07-25 | GSE263240 | GEO
Project description:Activation of the TLR4 signaling pathway by LPS leads to induction of both inflammatory and interferon-stimulated genes, however, the mechanisms through which these coordinately activated transcriptional programs are balanced to promote an optimal innate immune response remain poorly understood. In a genome-wide siRNA screen of the LPS-induced TNF- response in macrophages, we identified the interferon-stimulated protein IFIT1 as a negative regulator of the inflammatory gene program. Transcriptional profiling further identified an unexpected positive regulatory role for IFIT1 in type I interferon expression, implicating IFIT1 as a reciprocal modulator of LPS-induced gene classes. We demonstrate that these effects of IFIT1 are mediated through modulation of a Sin3A-HDAC2 transcriptional regulatory complex at LPS-induced gene loci. Beyond the well-studied role of cytosolic IFIT1 in restricting viral replication, our data demonstrate an unappreciated function for nuclear IFIT1 in differential transcriptional regulation of separate branches of the LPS-induced gene program.
2018-09-10 | GSE103829 | GEO