Injured adult neurons regress to an embryonic transcriptional growth state

Gunnar H. D. Poplawski (), Riki Kawaguchi, Erna Niekerk, Paul Lu, Neil Mehta, Philip Canete, Richard Lie, Ioannis Dragatsis, Jessica M. Meves, Binhai Zheng, Giovanni Coppola and Mark H. Tuszynski ()
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Gunnar H. D. Poplawski: University of California San Diego
Riki Kawaguchi: University of California Los Angeles
Erna Niekerk: University of California San Diego
Paul Lu: University of California San Diego
Neil Mehta: University of California San Diego
Philip Canete: University of California San Diego
Richard Lie: University of California San Diego
Ioannis Dragatsis: University of Tennessee
Jessica M. Meves: University of California San Diego
Binhai Zheng: University of California San Diego
Giovanni Coppola: University of California Los Angeles
Mark H. Tuszynski: University of California San Diego

Nature, 2020, vol. 581, issue 7806, 77-82

Abstract: Abstract Grafts of spinal-cord-derived neural progenitor cells (NPCs) enable the robust regeneration of corticospinal axons and restore forelimb function after spinal cord injury1; however, the molecular mechanisms that underlie this regeneration are unknown. Here we perform translational profiling specifically of corticospinal tract (CST) motor neurons in mice, to identify their ‘regenerative transcriptome’ after spinal cord injury and NPC grafting. Notably, both injury alone and injury combined with NPC grafts elicit virtually identical early transcriptomic responses in host CST neurons. However, in mice with injury alone this regenerative transcriptome is downregulated after two weeks, whereas in NPC-grafted mice this transcriptome is sustained. The regenerative transcriptome represents a reversion to an embryonic transcriptional state of the CST neuron. The huntingtin gene (Htt) is a central hub in the regeneration transcriptome; deletion of Htt significantly attenuates regeneration, which shows that Htt has a key role in neural plasticity after injury.

Date: 2020
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DOI: 10.1038/s41586-020-2200-5

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