Torretti, Elisabeth, 2017-2018

Elisabeth Torretti
Elisabeth
Torretti

"Fully Defined Differentiation of Medium Spiny Neurons from Human Induced Pluripotent Stem Cells"

Host Mentor: Jeanne Loring
Center for Regenerative Medicine, Scripps Research Institute

Recent advances in disease modeling with directed differentiation of induced pluripotent stem cells have offered alternatives to mouse models and given us the ability to understand disease on a cellular level. Familial Dyskinesia with Facial Myokymia (FDFM) is an autosomal dominant movement disorder. Characterized by involuntary twitches or tremors, FDFM has been causatively linked to several mutations in the adenylate cyclase 5 (ADCY5) gene, which is highly expressed in the striatum. Medium spiny neurons (MSNs), most well known for their role in Huntington’s disease, are the principal projection neurons of the striatum and the hypothesized affected cell type in FDFM. Previous MSN differentiation protocols reported enriched populations containing between 5-50% MSNs. Here we report an improved and fully defined method for MSN differentiation through stimulation of the TGF signaling pathway by Activin A. We have successfully direct human induced pluripotent stem cells (iPSCs) to enriched populations of 54% DARPP32+/CTIP2+ MSNs. Our findings allow for more efficient generation of MSNs from IPSCs for stem-cell based drug discovery and therapies.