Project description:An immortalized multipotent otic progenitor (iMOP) cell was generated by transient expression of c-Myc in Sox2-expressing otic progenitor cells. The procedure activated endogenous c-Myc expression in the cells and amplified existing Sox2-dependent transcripts to promote self-renewal. Downregulation of c-Myc expression following growth factor withdrawal resulted in a molecular switch from self-renewal to otic differentiation. ChIP-Seq was accomplished by immunoprecipitating endogenous RNA PolII, c-Myc and Sox2
Project description:An immortalized multipotent otic progenitor (iMOP) cell was generated by transient expression of c-Myc in Sox2-expressing otic progenitor cells. The procedure activated endogenous c-Myc expression in the cells and amplified existing Sox2-dependent transcripts to promote self-renewal. Downregulation of c-Myc expression following growth factor withdrawal resulted in a molecular switch from self-renewal to otic differentiation. Progenitor cells from embryonic inner ear that form otospheres were infected with a c-Myc retrovirus to promote self-renewal
Project description:An immortalized multipotent otic progenitor (iMOP) cell was generated by transient expression of c-Myc in Sox2-expressing otic progenitor cells. The procedure activated endogenous c-Myc expression in the cells and amplified existing Sox2-dependent transcripts to promote self-renewal. Downregulation of c-Myc expression following growth factor withdrawal resulted in a molecular switch from self-renewal to otic differentiation.
Project description:An immortalized multipotent otic progenitor (iMOP) cell was generated by transient expression of c-Myc in Sox2-expressing otic progenitor cells. The procedure activated endogenous c-Myc expression in the cells and amplified existing Sox2-dependent transcripts to promote self-renewal. Downregulation of c-Myc expression following growth factor withdrawal resulted in a molecular switch from self-renewal to otic differentiation.
Project description:Sox2 is a pleiotropic transcription factor that regulates self-renewal and differentiation capacity in different types of stem cells, raising the possibility that it regulates similar transcriptional programs controlling common stemness. Embryonic stem (ES) cells and trophoblast stem (TS) cells are two developmentally related types of stem cells, which originate from distinct lineages of peri-implantation embryos. We have found that Sox2 is a critical regulator of self-renewal in both of two stem cells. Genome-wide analysis of Sox2 target genes using Affymetrix Exon Arrays and chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) unraveled that it regulates distinct transcriptional networks in ES and TS cells. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
Project description:Other than in the development of the brain, SOX2 is essential for the long-term self-renewal of neural stem cells (NSCs). The mechanisms of how SOX2 maintains the stemness of NSCs is not yet understood. We have identified Fos as a downstream target of SOX2, and therefore used CUT&RUN to investigate where these transcription factors - and the c-FOS partner c-JUN - interact with the genome. By comparing binding patterns of c-FOS, c-JUN and SOX2, we find that they co-occupate the promoter of the SOCS3 locus, which we also have identified as a gene that rescues SOX2 deletion induced senescence when overexpressed in neurospheres grown from Sox2-deleted mouse NSCs. Taken together, our data provide a basis for elucidating a gene regulatory network necessary for the maintenance of self-renewal in post-embryonic neural stem cells.
Project description:The pluripotency transcription factor SOX2 is essential for the maintenance of glioblastoma stem cells (GSC), which drive tumor growth and treatment resistance.To understand how SOX2 is regulated in GSCs, we utilized a proteomic approach and identified the E3 ubiquitin ligase TRIM26 as a direct SOX2-interacting protein. Unexpectedly, we found TRIM26 depletion decreased SOX2 protein levels and increased SOX2 polyubiquitination in patient-derived GSCs, suggesting TRIM26 promotes SOX2 protein stability. Accordingly, TRIM26 knockdown reduced SOX2 transcriptional activity, self-renewal capacity, and in vivo tumorigenicity in multiple GSC lines. Mechanistically, we found TRIM26, via its C-terminal PRYSPRY domain, but independent of its RING domain, stabilizes SOX2 protein by directly inhibiting the interaction of SOX2 with WWP2, which we identify as a bona fide SOX2 E3 ligase in GSCs. Our work identifies E3 ligase competition as a critical mechanism of SOX2 regulation, with functional consequences for GSC identity and maintenance.
