Direct Lineage Reprogramming for Brain Repair: Breakthroughs and Challenges

Injury to the human central nervous system (CNS) is devastating because our adult mammalian brain lacks intrinsic regenerative capacity to replace lost neurons and induce functional recovery. An emerging approach towards brain repair is to instruct fate conversion of brain-resident non-neuronal cells into induced neurons (iNs) by direct lineage reprogramming. Considerable progress has been made in converting various source cell types of mouse and human origin into clip ically relevant iNs. Recent achievements using transcriptomics and epigenetics have shed light on the molecular mechanisms underpinning neuronal reprogramming, while the potential capability of iNs in promoting functional recovery in pathological contexts has started to be evaluated. Although future challenges need to be overcome before clinical translation, lineage reprogramming holds promise for effective cell-replacement therapy in regenerative.