研究セミナー Epigenetic regulation in the mammalian subventricular zone brain stem cell niche

Quiescent tissue specific stem cells become activated to generate rapidly proliferating transit amplifying progenitors (TAPs). The mechanisms maintaining neural stem cell (NSC) quiescence versus TAP proliferation in health and in cancer remain unclear. Isocitrate dehydrogenase 1 R132H mutations drive the growth of human gliomas. To model this, we conditionally expressed Idh1R132H in the subventricular zone (SVZ) of the adult mouse brain. Stem and transit amplifying/progenitor cells expanded and proliferation increased. SVZ cells infiltrated into surrounding brain regions. This mouse model shows that the Idh1R132H mutation drive a gliomagenic phenotype in the major adult neurogenic stem cell niche. We hypothesized that distinct epigenetic complex subunit expression and molecular targeting segregates their function in NSC versus TAPs. Our work reveals distinct Eed expression, molecular targets and functions upstream in the SVZ lineage from Ezh2, and provides novel targets for clinical therapeutics. Thus w ehave uncovered two disting and novel regulations of neurogenic stem cells.