Comparative transcriptomic analysis of sprouting and regenerating corticospinal neurons

Abstract
The corticospinal tract (CST) is a critical motor system in humans for voluntary movement. The inability of adult corticospinal axons to spontaneously regenerate after spinal cord injury (SCI) may be attributable in part to incomplete activation of neuronal growth programs after injury. Recently we reported that robust corticospinal regeneration can be elicited in neural stem cell (NSC) grafts implanted into sites of injury (Kadoya et al., Nat Med 2016). To gain insight into intrinsic corticospinal neuronal mechanisms associated with successful regeneration, we performed transcriptomic analysis of regenerating corticospinal neurons. In a second study, we performed complimentary transcriptomic analysis on CST neurons in which compensatory regenerative sprouting was triggered by a unilateral pyramidotomy. Bioinformatic data mining and gene regulatory network analysis of both datasets revealed several master regulatory hub genes that are converging in both models. We are now testing several of these potential master regulators of regeneration in in vitro and in vivo models of spinal cord injury.

Authors
*G. H. POPLAWSKI1, K. KHOO1, N. MEHTA1, R. KAWAGUCHI2, E. ROSENZWEIG1, K. KADOYA1, P. LU1, G. COPPOLA2, M. TUSZYNSKI1;
1Neurosci., Univ. of California San Diego, La Jolla, CA; 2Departments of Psychiatry & Neurol., UC Los Angeles, Los Angeles, CA
Disclosures
G.H. Poplawski: None. K. Khoo: None. N. Mehta: None. R. Kawaguchi: None. E. Rosenzweig: None. K. Kadoya: None. P. Lu: None. G. Coppola: None. M. Tuszynski: None.

LINK: Session 142 – Mechanisms in Spinal Cord Injury

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