A single factor elicits multilineage reprogramming of astrocytes in the adult mouse striatum
Yunjia Zhang, Boxun Li, Sergio Cananzi, Chuanhui Han, Leilei Wang, Yuhua Zou, Yang‐Xin Fu, Gary C. Hon, Chunli Zhang
Abstract
SignificanceOutside the neurogenic niches, the adult brain lacks multipotent progenitor cells. In this study, we performed a series of in vivo screens and reveal that a single factor can induce resident brain astrocytes to become induced neural progenitor cells (iNPCs), which then generate neurons, astrocytes, and oligodendrocytes. Such a conclusion is supported by single-cell RNA sequencing and multiple lineage-tracing experiments. Our discovery of iNPCs is fundamentally important for regenerative medicine since neural injuries or degeneration often lead to loss/dysfunction of all three neural lineages. Our findings also provide insights into cell plasticity in the adult mammalian brain, which has largely lost the regenerative capacity.