Direct neuronal reprogramming: Fast forward from new concepts toward therapeutic approaches

Differentiated cells have long been considered fixed in their identity. However, about 20 years ago, the first direct conversion of glial cells into neurons in vitro opened the field of direct neuronal reprogramming.Since then, neuronal reprogramming has achieved the generation of fully functional, mature neurons with remarkable efficiency, even in diseased brain environments. Beyond their clinical implications, these discoveries provided basic insights into crucial mechanisms underlying conversion of specific cell types into neurons and maintenance of neuronal identity. Here we discuss such principles, including the importance of the starter cell for shaping the outcome of neuronal reprogramming. We further highlight technical concerns for in vivo reprogramming and propose a code of conduct to avoid artifacts and pitfalls. We end by pointing out next challenges for development of less invasive cell replacement therapies for humans.

Automated summary

A successful experiment conducted 20 years ago opened up the field of neuronal reprogramming, which has since made significant progress. These studies are not only important for clinical applications, but also provide fundamental insights into the mechanisms of cell conversion into neurons and the maintenance of neuronal identity.