[PDF][PDF] Enhanced neuronal regeneration in the CAST/Ei mouse strain is linked to expression of differentiation markers after injury

V Lisi, B Singh, M Giroux, E Guzman, MW Painter… - Cell reports, 2017 - cell.com
V Lisi, B Singh, M Giroux, E Guzman, MW Painter, YC Cheng, E Huebner, G Coppola…
Cell reports, 2017cell.com
Peripheral nerve regeneration after injury requires a broad program of transcriptional
changes. We investigated the basis for the enhanced nerve regenerative capacity of the
CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia
(DRG) showed a CAST/Ei-specific upregulation of Ascl1 after injury. Ascl1 overexpression in
DRG neurons of C57BL/6 mice enhanced their neurite outgrowth. Ascl1 is regulated by miR-
7048-3p, which is downregulated in CAST/Ei mice. Inhibition of miR-7048-3p enhances …
Summary
Peripheral nerve regeneration after injury requires a broad program of transcriptional changes. We investigated the basis for the enhanced nerve regenerative capacity of the CAST/Ei mouse strain relative to C57BL/6 mice. RNA sequencing of dorsal root ganglia (DRG) showed a CAST/Ei-specific upregulation of Ascl1 after injury. Ascl1 overexpression in DRG neurons of C57BL/6 mice enhanced their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is downregulated in CAST/Ei mice. Inhibition of miR-7048-3p enhances neurite outgrowth. Following injury, CAST/Ei neurons largely retained their mature neuronal profile as determined by single-cell RNA- seq, whereas the C57BL/6 neurons acquired an immature profile. These findings suggest that one facet of the enhanced regenerative phenotype is preservation of neuronal identity in response to injury.
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