کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2093571 | 1081967 | 2015 | 15 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: SOX2 Reprograms Resident Astrocytes into Neural Progenitors in the Adult Brain SOX2 Reprograms Resident Astrocytes into Neural Progenitors in the Adult Brain](/preview/png/2093571.png)
• SOX2 induces ASCL1-positive neural progenitors in the adult mouse brain
• Ascl1 in resident astrocytes is required for SOX2-mediated in vivo reprogramming
• Induced ASCL1-positive neural progenitors generate mature calretinin neurons
SummaryGlial 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.
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Journal: - Volume 4, Issue 5, 12 May 2015, Pages 780–794