Anna Eastman is a postdoctoral scholar in stem cell biology and regenerative medicine. She will present her work on characterizing postnatal human neural stem cells and their role in brain disease.
Prior work in the Weissman Lab characterized fetal human neural stem cells (NSCs) of the central nervous system (CNS). However, postnatal human NSCs remain far less characterized. Although adult neurogenesis is well-understood in rodents and other mammals, its existence in the adult human brain is widely disputed. Using single-cell transcriptomics, we aim to uncover new markers to identify and isolate NSCs from fresh postnatal human brain tissue. We will use lineage tracing to demonstrate multilineage differentiation potential in live cell assays both in vitro and in vivo, by intracranial transplantation of candidate human NSCs into mice. Furthermore, we aim to explore the involvement of NSCs and downstream progenitors in pediatric epilepsy caused by hemimegalencephaly (HME), a condition characterized by overgrowth of an entire cerebral hemisphere. Clonal somatic mutations arising in the stem cell pool can have outsized and lasting consequences for tissue health compared to similar mutations occurring in terminally differentiated cells. Hyper-competitive mutant stem cells have been known to drive progressive pathology in numerous adult tissues. Because activating mutations in the mammalian target of rapamycin (mtor) pathway underlie HME, we aim to define the modes of intercellular competition promoting pathological mtor-mutant NSC expansion as well as demonstrate its ongoing relevance postnatally, in the hopes of revealing novel therapeutic targets for the alleviation of seizure symptoms.