Induction of oligodendrocyte lineage cells by direct cellular reprogramming.
Clinical Neurology; Neurosurgery and Neuroradiology
Final Report Abstract
The large-scale manufacture of mature human cell types from easily accessible and renewable sources is required for several key applications of regenerative medicine, including disease modelling, drug discovery, and cell transplantation. However, the isolation or in vitro derivation of many highly desirable human cells for regenerative medicine, including oligodendrocytes, remains challenging, poorly reproducible and inefficient. During my DFG research fellowship, I first optimised inducible transgene overexpression in human pluripotent stem cells. The optimised overexpression system was based on a dual genomic safe harbour targeting strategy of the Tet-ON system into the human ROSA26 and AAVS1 locus. Subsequently, I used the targeted inducible overexpression system to generate stable hPSC lines carrying the inducible master reprogramming factors MYOD1, NEUROG2, and OLIG2+SOX10, respectively. These lines served as inexhaustible source for the highly scalable, rapid, single step, virus-free, chemically defined, fully reproducible and deterministic forward programing into skeletal myocytes, excitatory cortical neurons, and oligodendrocytes, respectively.
