Lineage Reprogramming of Astroglial Cells from Different Origins into Distinct Neuronal Subtypes

Highlights

• ASCL1 or NEUROG2 converts cerebellum astroglia into functional induced neurons (iNs)

• Cerebral cortex and cerebellum astroglia generate different subtypes of iNs in vitro

• iNs integrate as pyramidal-like cells after transplantation in the cerebral cortex

• iNs integrate as granular- and periglomerular-like neurons in the olfactory bulb

Summary

Astroglial cells isolated from the rodent postnatal cerebral cortex are particularly susceptible to lineage reprogramming into neurons. However, it remains unknown whether other astroglial populations retain the same potential. Likewise, little is known about the fate of induced neurons (iNs) in vivo. In this study we addressed these questions using two different astroglial populations isolated from the postnatal brain reprogrammed either with Neurogenin-2 (Neurog2) or Achaete scute homolog-1 (Ascl1). We show that cerebellum (CerebAstro) and cerebral cortex astroglia (CtxAstro) generates iNs with distinctive neurochemical and morphological properties. Both astroglial populations contribute iNs to the olfactory bulb following transplantation in the postnatal and adult mouse subventricular zone. However, only CtxAstro transfected with Neurog2 differentiate into pyramidal-like iNs after transplantation in the postnatal cerebral cortex. Altogether, our data indicate that the origin of the astroglial population and transcription factors used for reprogramming, as well as the region of integration, affect the fate of iNs.