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 journalArticlepeer-review

98 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)780-794
Number of pages15
JournalStem Cell Reports
Volume4
Issue number5
DOIs
StatePublished - May 12 2015

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'SOX2 reprograms resident astrocytes into neural progenitors in the adult brain'. Together they form a unique fingerprint.

Cite this