SOX2 Reprograms Resident Astrocytes into Neural Progenitors in the Adult Brain

作者：Niu Wenze; Zang Tong; Smith Derek K; Vue Tou Yia; Zou Yuhua; Bachoo Robert; Johnson Jane E; Zhang Chun Li^*

来源：Stem Cell Reports, 2015, 4(5): 780-794.

DOI：10.1016/j.stemcr.2015.03.006

Glial cells can be in vivo reprogrammed into functional neurons in the adult CNS; however, the process by which this reprogramming occurs is unclear. Here, we show that a distinct cellular sequence is involved in SOX2-driven in situ conversion of adult astrocytes to neurons. This includes ASCL1(+) neural progenitors and DCX+ adult neuroblasts (iANBs) as intermediates. Importantly, ASCL1 is required, but not sufficient, for the robust generation of iANBs in the adult striatum. These progenitor-derived iANBs predominantly give rise to calretinin(+) interneurons when supplied with neurotrophic factors or the small-molecule valproic acid. Patch-clamp recordings from the induced neurons reveal subtype heterogeneity, though all are functionally mature, fire repetitive action potentials, and receive synaptic inputs. Together, these results show that SOX2-mediated in vivo reprogramming of astrocytes to neurons passes through proliferative intermediate progenitors, which may be exploited for regenerative medicine.

• 出版日期2015-5-12