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Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair

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Listed:
  • Vishnu Muraleedharan Saraswathy

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Lili Zhou

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

  • Mayssa H. Mokalled

    (Washington University School of Medicine
    Washington University School of Medicine
    Washington University School of Medicine)

Abstract

Adult zebrafish have an innate ability to recover from severe spinal cord injury. Here, we report a comprehensive single nuclear RNA sequencing atlas that spans 6 weeks of regeneration. We identify cooperative roles for adult neurogenesis and neuronal plasticity during spinal cord repair. Neurogenesis of glutamatergic and GABAergic neurons restores the excitatory/inhibitory balance after injury. In addition, a transient population of injury-responsive neurons (iNeurons) show elevated plasticity 1 week post-injury. We found iNeurons are injury-surviving neurons that acquire a neuroblast-like gene expression signature after injury. CRISPR/Cas9 mutagenesis showed iNeurons are required for functional recovery and employ vesicular trafficking as an essential mechanism that underlies neuronal plasticity. This study provides a comprehensive resource of the cells and mechanisms that direct spinal cord regeneration and establishes zebrafish as a model of plasticity-driven neural repair.

Suggested Citation

  • Vishnu Muraleedharan Saraswathy & Lili Zhou & Mayssa H. Mokalled, 2024. "Single-cell analysis of innate spinal cord regeneration identifies intersecting modes of neuronal repair," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50628-y
    DOI: 10.1038/s41467-024-50628-y
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    1. Elizabeth J. Bradbury & Lawrence D. F. Moon & Reena J. Popat & Von R. King & Gavin S. Bennett & Preena N. Patel & James W. Fawcett & Stephen B. McMahon, 2002. "Chondroitinase ABC promotes functional recovery after spinal cord injury," Nature, Nature, vol. 416(6881), pages 636-640, April.
    2. Shobana V. Stassen & Gwinky G. K. Yip & Kenneth K. Y. Wong & Joshua W. K. Ho & Kevin K. Tsia, 2021. "Generalized and scalable trajectory inference in single-cell omics data with VIA," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    3. Mohamed A. El-Brolosy & Zacharias Kontarakis & Andrea Rossi & Carsten Kuenne & Stefan Günther & Nana Fukuda & Khrievono Kikhi & Giulia L. M. Boezio & Carter M. Takacs & Shih-Lei Lai & Ryuichi Fukuda &, 2019. "Genetic compensation triggered by mutant mRNA degradation," Nature, Nature, vol. 568(7751), pages 193-197, April.
    4. Michael V. Sofroniew, 2018. "Dissecting spinal cord regeneration," Nature, Nature, vol. 557(7705), pages 343-350, May.
    5. Yingyao Zhou & Bin Zhou & Lars Pache & Max Chang & Alireza Hadj Khodabakhshi & Olga Tanaseichuk & Christopher Benner & Sumit K. Chanda, 2019. "Metascape provides a biologist-oriented resource for the analysis of systems-level datasets," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    6. Chun-Xiao Huang & Yacong Zhao & Jie Mao & Zhen Wang & Lulu Xu & Jianwei Cheng & Na N. Guan & Jianren Song, 2021. "An injury-induced serotonergic neuron subpopulation contributes to axon regrowth and function restoration after spinal cord injury in zebrafish," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    7. Daniel Wehner & Themistoklis M. Tsarouchas & Andria Michael & Christa Haase & Gilbert Weidinger & Michell M. Reimer & Thomas Becker & Catherina G. Becker, 2017. "Wnt signaling controls pro-regenerative Collagen XII in functional spinal cord regeneration in zebrafish," Nature Communications, Nature, vol. 8(1), pages 1-17, December.
    8. Mark A. Anderson & Timothy M. O’Shea & Joshua E. Burda & Yan Ao & Sabry L. Barlatey & Alexander M. Bernstein & Jae H. Kim & Nicholas D. James & Alexandra Rogers & Brian Kato & Alexander L. Wollenberg , 2018. "Required growth facilitators propel axon regeneration across complete spinal cord injury," Nature, Nature, vol. 561(7723), pages 396-400, September.
    9. Wei Zhao & Kevin G. Johnston & Honglei Ren & Xiangmin Xu & Qing Nie, 2023. "Inferring neuron-neuron communications from single-cell transcriptomics through NeuronChat," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    10. Benjamin Lacar & Sara B. Linker & Baptiste N. Jaeger & Suguna Rani Krishnaswami & Jerika J. Barron & Martijn J. E. Kelder & Sarah L. Parylak & Apuã C. M. Paquola & Pratap Venepally & Mark Novotny & Ca, 2016. "Nuclear RNA-seq of single neurons reveals molecular signatures of activation," Nature Communications, Nature, vol. 7(1), pages 1-13, April.
    11. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    12. Julia Kolb & Vasiliki Tsata & Nora John & Kyoohyun Kim & Conrad Möckel & Gonzalo Rosso & Veronika Kurbel & Asha Parmar & Gargi Sharma & Kristina Karandasheva & Shada Abuhattum & Olga Lyraki & Timon Be, 2023. "Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
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