Enhanced Neuronal Regeneration in the CAST/Ei Mouse Strain Is Linked to Expression of Differentiation Markers after Injury

Publication date: 1 August 2017
Source:Cell Reports, Volume 20, Issue 5
Author(s): Véronique Lisi, Bhagat Singh, Michel Giroux, Elmer Guzman, Michio W. Painter, Yung-Chih Cheng, Eric Huebner, Giovanni Coppola, Michael Costigan, Clifford J. Woolf, Kenneth S. Kosik
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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Teaser

Lisi et al. find that increased Ascl1 expression is associated with the superior regenerative capacity of CAST/Ei mice. Single-cell RNA-seq demonstrated that CAST/Ei mice retained more mature neurons after injury than did C57BL/6 mice, thereby suggesting that genetic drivers of the enhanced regenerative phenotype include mechanisms to preserve neuronal identity after injury.


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