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Injured adult neurons regress to an embryonic transcriptional growth state
Abstract
Grafts of spinal-cord-derived neural progenitor cells (NPCs) enable the robust regeneration of corticospinal axons and restore forelimb function after spinal cord injury 1; 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.
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“Injury is a well-established trigger of cellular de-differentiation, and the changes we observed are likely a consequence of human neurons adhering to this principle (Gu et al., 2020; Jopling et al., 2010; Poplawski et al., 2020; Renthal et al., 2020; Tzahor and Poss, 2017; Wagner et al., 2017).”
From Age-dependent instability of mature neuronal fate in induced neurons from Alzheimer’s patients (2021) · cites this paper as Poplawski et al., 2020
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Metadata
- Authors
- Poplawski, G. H. D., Kawaguchi, R., Van Niekerk, E., Lu, P., Mehta, N., Canete, P., Lie, R., Dragatsis, I., Meves, J. M., Zheng, B., Coppola, G., & Tuszynski, M. H.
- Affiliations
- University of California San Diego (US)
- University of California, Los Angeles (US)
- United States Department of Veterans Affairs (US)
- Corresponding author
- Poplawski, Gunnar H. D.
- Tuszynski, Mark H.
- ORCID
- Venue
- Nature
- Published
- 2020-04-15
- Volume
- 581
- Issue
- 7806
- Pages
- 77-82
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W3016778275
- Cited by
- 247
- References
- 55
- Citations by year
- 2026: 19 · 2025: 39 · 2024: 41 · 2023: 53 · 2022: 42 · 2021: 33 · 2020: 19
- FWCI
- 16.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 RX002264)
- National Institute of Neurological Disorders and Stroke (P30NS062691)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- spinal cord injury, axon regeneration, huntingtin, neuroplasticity
- MeSH terms
- Huntingtin Protein, RNA-Seq, Animals, Axons, Disease Models, Animal, Embryo, Mammalian, Female, Nerve Regeneration, Neuronal Plasticity, Neurons, Pyramidal Tracts, Spinal Cord Injuries, Transcription, Genetic, Protein Biosynthesis, Gene Expression Profiling, Cell Proliferation, Mice, Neural Stem Cells, Transcriptome
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