Expression level of the reprogramming factor NeuroD1 is critical for neuronal conversion efficiency from different cell types

Abstract

Several transcription factors, including NeuroD1, have been shown to act as neuronal reprogramming factors (RFs) that induce neuronal conversion from somatic cells. However, it remains unexplored whether expression levels of RFs in the original cells affect reprogramming efficiency. Here, we show that the neuronal reprogramming efficiency from two distinct glial cell types, microglia and astrocytes, is substantially dependent on the expression level of NeuroD1: low expression failed to induce neuronal reprogramming, whereas elevated NeuroD1 expression dramatically improved reprogramming efficiency in both cell types. Moreover, even under conditions where NeuroD1 expression was too low to induce effective conversion by itself, combined expression of three RFs (Ascl1, Brn2, and NeuroD1) facilitated the breaking down of cellular barriers, inducing neuronal reprogramming. Thus, our results suggest that a sufficiently high expression level of RFs or alternatively their combinatorial expression, is the key to achieving efficient neuronal reprogramming from different cells. Highlights{blacksquare} High expression of NeuroD1 is required for neuronal conversion. {blacksquare}Multiple infections with NeuroD1-expressing virus enhance neuronal reprogramming {blacksquare}Combinatorial expression of NeuroD1 with other RFs facilitates neuronal conversion eTOC blurbIn this article, Matsuda-Ito et al. demonstrate that the efficacy of conversion into neurons from two distinct glial cells, microglia and astrocytes, depends on the NeuroD1 expression level. They also show that increased NeuroD1 expression alone enables efficient neuronal reprogramming in non-reactive astrocytes that were previously shown to be difficult to convert into neurons.