Transcription factor-induced lineage selection of stem-cell-derived neural progenitor cells

Abstract

The generation of specific types of neurons from stem cells offers important opportunities in regenerative medicine. However, future applications and proper verification of cell identities will require stringent ways to generate homogeneous neuronal cultures. Here we show that transcription factors like Lmx1a, Phox2b, Nkx2.2, and Olig2 can induce desired neuronal lineages from most expressing neural progenitor cells by a mechanism resembling developmental binary cell-fate switching. Such efficient selection of cell fate resulted in remarkable cellular enrichment that enabled global gene-expression validation of generated neurons and identification of previously unrecognized features in the studied cell lineages. Several sources of stem cells have a limited competence to differentiate into specific neuronal cell types; e.g., dopamine neurons. However, we show that the combination of factors that normally promote either regional or dedicated neuronal specification can overcome limitations in cellular competence and also promote efficient reprogramming in more remote neural contexts, including human neural progenitor cells.