Project description:Alpha-cell-derived INS+ cells (yellow cells) were isolated 1 month after AAV-PM (adeno-associated virus carrying pdx1 and mafA under the CMV promoter) infusion from ALX-treated GCG-Cre; R26RTomato; MIP-GFP mice, based on expression of tomato red (alpha-cell lineage) and GFP by flow cytometry. Sorted normal GFP+ beta cells and normal TOM+ alpha cells from GCG-Cre; R26RTomato; MIP-GFP mice without any treatment were used as controls.
Project description:FAM46C is one of the most frequently mutated genes in multiple myeloma (MM). Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into MM cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induces cell death. Moreover, silencing of FAM46C in MM cells expressing WT protein enhance cell proliferation. Finally, using a FAM46C-FLAG knock-in mouse strain we show that the FAM46C protein is strongly induced during activation of primary splenocytes and that B lymphocytes isolated from newly generated FAM46C KO mice proliferate faster than those isolated from their WT littermates. Concluding, our data clearly indicate that FAM46C works as an onco-suppressor, with the specificity for B-lymphocyte lineage from which multiple myeloma originates.
Project description:LSKs(lineage-, Sca-1+, c-kit+ cells) in the bone marrow from normal and 5-Fluorouracil (5-FU) treated (Day 9) wild type (WT) and Tespa1-knockout (KO) mice were isolated to explore the differentially expressed genes by RNA-seq.