Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons

Nolbrant S., Giacomoni J., Hoban D.B, Bruzelius A., Birtele M., Chandler-Militello D., Pereira M., Rylander Ottosson D., Goldman S.A., Parmar M.

Stem Cell Reports, 2020

Human glial progenitor cells (hGPCs) are promising cellular substrates to explore for the in situ production of new neurons for brain repair. Proof of concept for direct neuronal reprogramming of glial progenitors using human cells has been difficult to perform since hGPCs are born late during human fetal development, with limited accessibility for in vitro culture. In this study, the authors provide evidence that hGPCs isolated from both the human fetal brain and differentiated from hESCs can be successfully reprogrammed into functional iNs, including induced DA neurons (iDANs). They also establish a renewable and reproducible stem cell-based hGPC system for direct neural conversion in vitro. Using this system, they have identified optimal combinations of fate determinants for the efficient dopaminergic (DA) conversion of hGPCs, thereby yielding a therapeutically relevant cell type that selectively degenerates in Parkinson’s disease.