PT - JOURNAL ARTICLE AU - Lisi, Véronique AU - Singh, Bhagat AU - Giroux, Michel AU - Guzman, Elmer AU - Painter, Michio W AU - Cheng, Yung-Chih AU - Huebner, Eric AU - Coppola, Giovanni AU - Costigan, Michael AU - Woolf, Clifford J. AU - Kosik, Kenneth S TI - Enhanced neuronal regeneration in the CAST/Ei mouse strain is linked to expression of differentiation markers after injury AID - 10.1101/160366 DP - 2017 Jan 01 TA - bioRxiv PG - 160366 4099 - http://biorxiv.org/content/early/2017/07/06/160366.short 4100 - http://biorxiv.org/content/early/2017/07/06/160366.full AB - 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 C57BL/6 mice DRG neurons enhanced their neurite outgrowth. Ascl1 is regulated by miR-7048-3p, which is down-regulated 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 RNAseq, 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.