In vivo Chemical Reprogramming of Astrocytes into Functional Neurons

In mammals, many organs lack robust regenerative abilities. Lost cells in impaired tissue could potentially be compensated by converting nearby cells in situ through in vivo reprogramming. Small molecule-induced reprogramming offers a spatiotemporally flexible and non-integrative strategy for altering cell fate, which is, in principle, favorable for in vivo reprogramming in organs with notoriously poor regenerative abilities, such as the brain. Here, we demonstrate that in adult mouse brain, small molecules can reprogram astrocytes into functional neurons. The in situ chemically induced neurons resemble endogenous neurons in gene expression profiles, electrophysiological properties and synaptic connectivity. Our study demonstrates, for the first time, in vivo chemical reprogramming in the adult brain and provides a novel approach for developing neuronal replacement therapies. Overall design: The mouse chemical induced neurons at BW12 were selected for single-cell RNA-seq.