SOX2 Reprograms Resident Astrocytes into Neural Progenitors in the Adult Brain

Wenze Niu, Tong Zang, Derek K. Smith, Tou Yia Vue, Yuhua Zou, Robert Bachoo, Jane E. Johnson, Chun Li Zhang

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Glial cells can be invivo 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 insitu conversion of adult astrocytes to neurons. This includes ASCL1<sup>+</sup> neural progenitors and DCX<sup>+</sup> 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<sup>+</sup> 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 invivo reprogramming of astrocytes to neurons passes through proliferative intermediate progenitors, which may be exploited for regenerative medicine. In this article, Zhang and colleagues reveal that SOX2-mediated invivo reprogramming of adult astrocytes transits through ASCL1-positive neural progenitors. These progenitors further generate DCX-positive neuroblasts and functionally mature neurons in the adult mouse striatum. This stepwise and expandable invivo reprogramming process may be exploited for neural regeneration by using resident glial cells.

Original languageEnglish (US)
JournalStem Cell Reports
DOIs
StateAccepted/In press - Jan 20 2015

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Developmental Biology
  • Genetics

Cite this