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SOX2 reprograms resident astrocytes into neural progenitors in the adult brain.


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.

SUBMITTER: Niu W 

PROVIDER: S-EPMC4437485 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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SOX2 reprograms resident astrocytes into neural progenitors in the adult brain.

Niu Wenze W   Zang Tong T   Smith Derek K DK   Vue Tou Yia TY   Zou Yuhua Y   Bachoo Robert R   Johnson Jane E JE   Zhang Chun-Li CL  

Stem cell reports 20150423 5


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-  ...[more]

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