Project description:Glioblastoma is a primary brain cancer with a near 100% recurrence rate. Upon recurrence, the tumor is resistant to all conventional therapies, and because of this, 5-year survival is dismal. One of the major drivers of this high recurrence rate is the ability of GBM cells to adapt to complex changes within the tumor microenvironment. To elucidate the molecular mechanisms of this adaptation, specifically during chemotherapy, we employed ChIP-Sequencing and gene expression analysis. We identified a molecular circuit in which the expression of ciliary protein ALR13B is epigenetically regulated to promote adaptation to chemotherapy. Immuno-precipitation combined with Liquid Chromatography-Mass Spectrometry binding partner analysis revealed that that ARL13B interacts with the purine biosynthetic enzyme IMPDH2. Further, radioisotope tracing revealed that this interaction function as a negative regulator for purine salvaging. Inhibition of ARL13B-IMPDH2 interaction enhances temozolomide (TMZ)-induced DNA damage by forcing GBM cells to rely on the purine salvage pathway. Targeting the ARLI3B-IMPDH2 circuit can be achieved by using an FDA-approved drug, Mycophenolate Mofetil, that can block the IMPDH2 activity and enhance the therapeutic efficacy of TMZ. Our results suggest and support clinical evaluation of MMF in combination with TMZ treatment in glioma patients.
Project description:Gut microbiota is closely related to type 2 diabetes mellitus (T2DM). The gut microbiota of patients with T2DM is significantly different from that of healthy subjects in terms of bacterial composition and diversity. Here, we used the fermentation products of Paenibacillus bovis sp. nov. BD3526 to study the disease progression of T2DM in Goto-kakisaki (GK) rats. We found that the symptoms in GK rats fed the fermentation products of BD3526 were significantly improved. The 16S rRNA sequencing showed that the fermentation products of BD3526 had strong effects on the gut microbiota by increasing the content of Akkermansia. In addition, the interaction of the genus in the gut of the BD3526 group also significantly changed. Additional cytokine detection revealed that the fermentation products of BD3526 can reduce the inflammatory factors in the intestinal mucus of GK rats and thereby inhibit the inflammatory response and ameliorate the symptoms of T2DM.
Project description:This series is an updated dataset consisting of the Spec-seq and Methyl-Spec-seq samples for human CTCF with a bigger sequencing libraries and different epigenetic modifications. Each sample has replicate to gurantee the reproducibility for each measurement.