Astrocyter i subpiala zonen som ursprung till gliom i hjärnbarken

Tidsperiod: 2015-01-01 till 2017-06-30

Projektledare: Hanna Sabelström

Finansiär: Vetenskapsrådet

Bidragstyp: Projektbidrag

Budget: 3 150 000 SEK

Astrocytes, the most abundant cell population in the brain, show temporal and regional heterogeneity. Astrocytomas, the most common primary malignant brain tumor in adult patients, are often localized to cortical regions. Transcriptomal profiling has identified molecularly distinct subgroups of grade II-IV astrocytomas that associate with age and location. Murine astrocytoma models show that a population of neurogenic astrocytes in the subventricular zone (SVZ) can give rise to astrocytomas. It remains unknown if cortical astrocytomas originate from dedifferentiated astrocytes, SVZ astrocytes, or a yet undefined population of astrocyte precursors. Studies suggest that astrocyte precursors reside in the subpial zone (SPZ) of the developing cortex. We hypothesize that SPZ astrocytes represent a novel population of neural precursors and a source of cortical astrocytomas. We will characterize SPZ astrocytes and their niche in mouse and human brain. Fate-mapping with transgenic and virus-based mouse models will determine the origin of SPZ precursors. We will study transformation of SPZ astrocytes in response to RAS oncogenes and loss of tumor suppressor genes. We will compare transcriptomal profiles of SPZ astrocytes, murine astrocytomas, and human tumors to stratify the transcriptomal signature of cortical astrocytomas. The existence of a population of SPZ astrocyte precursors has profound implications for both regenerative medicine and the outcome of astrocytoma patients.