TRANsCre-DIONE transdifferentiates scar-forming reactive astrocytes into functional motor neurons [article]

Heeyoung An, Hye-Lan Lee, Doo-Wan Cho, Jinpyo Hong, Hye Yeong Lee, Jung Moo Lee, Junsung Woo, Jaekwang Lee, MinGu Park, Young-Su Yang, Su-Cheol Han, Yoon Ha (+1 others)
2020 bioRxiv   pre-print
In spinal cord injury (SCI), the scar-forming reactive astrocytes with upregulated GFAP proliferate aberrantly near the injury site, allowing themselves as a prime target for transdifferentiation into neurons to replenish dead neurons. However, the conventional use of GFAP promoter to target reactive astrocytes has two inherent problems: inadvertent conversion of normal astrocytes and low efficiency due to progressive weakening of promoter activity during transdifferentiation. Here, we report
more » ... at the scar-forming reactive astrocytes are selectively transdifferentiated into neurons with 87% efficiency and 96% specificity via TRANsCre-DIONE, a combination of the split-Cre system under two different promoters of GFAP and Lcn2 and a Cre-loxP-dependent inversion and expression of Neurog2 under the strong EF1α promoter. After SCI, TRANsCre-DIONE caused transdifferentiation into Isl1-positive motor neurons, reduced astrogliosis, enhanced regeneration in surrounding cells, and a significant motor recovery. Our study proposes TRANsCre-DIONE as the next-generation therapeutic approach for patients suffering from SCI.
doi:10.1101/2020.07.24.215160 fatcat:bt4whccpyrhilehqqv6slrhqgm