Biphasic inflammation control by dedifferentiated fibroblasts enables axon regeneration after spinal cord injury in zebrafish Article Swipe
Nora John
,
Thomas Fleming
,
Julia Kolb
,
Olga Lyraki
,
Sebastián Vásquez-Sepúlveda
,
Asha Parmar
,
Kyoohyun Kim
,
Maria Tarczewska
,
Kanwarpal Singh
,
Fédérico Marini
,
Sumeet Pal Singh
,
Sven Falk
,
Kristian Franze
,
Jochen Guck
,
Daniel Wehner
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.01.27.635043
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.01.27.635043
Fibrosis and persistent inflammation are interconnected processes that inhibit axon regeneration in the mammalian central nervous system (CNS). In zebrafish, by contrast, fibroblast-derived extracellular matrix deposition and inflammation facilitate regeneration. However, the regulatory cross-talk between fibroblasts and the innate immune system in the regenerating CNS is not understood. Here, we show that zebrafish fibroblasts possess a dual role in inducing and subsequently resolving inflammation, which are both essential for regeneration. We identify a transient, injury-specific cthrc1a + fibroblast state with an inflammation-associated, less differentiated, and non-fibrotic profile. Induction of this fibroblast state precedes and contributes to the initiation of the inflammatory response. At the peak of neutrophil influx, cthrc1a + fibroblasts coordinate the resolution of inflammation. Disruption of these inflammation dynamics inhibits axon regeneration and alters the mechano-structural properties of the lesion environment. This establishes the biphasic inflammation control by dedifferentiated fibroblasts as a pivotal mechanism for CNS regeneration. ONE SENTENCE SUMMARY Dedifferentiated fibroblasts sequentially induce and resolve neutrophil-driven inflammation through cytokine release to facilitate axon regeneration after spinal cord injury in zebrafish. HIGHLIGHTS Time-resolved single-cell transcriptomics of zebrafish spinal cord regeneration. Spinal cord injury induces fibroblast dedifferentiation. Dedifferentiated fibroblasts sequentially induce and resolve inflammation. Dysregulation of inflammation dynamics alters mechano-structural tissue properties.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.01.27.635043
- OA Status
- green
- Cited By
- 1
- References
- 158
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
Raw OpenAlex JSON
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- DOI
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https://doi.org/10.1101/2025.01.27.635043Digital Object Identifier
- Title
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Biphasic inflammation control by dedifferentiated fibroblasts enables axon regeneration after spinal cord injury in zebrafishWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-01-27Full publication date if available
- Authors
-
Nora John, Thomas Fleming, Julia Kolb, Olga Lyraki, Sebastián Vásquez-Sepúlveda, Asha Parmar, Kyoohyun Kim, Maria Tarczewska, Kanwarpal Singh, Fédérico Marini, Sumeet Pal Singh, Sven Falk, Kristian Franze, Jochen Guck, Daniel WehnerList of authors in order
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https://doi.org/10.1101/2025.01.27.635043Publisher landing page
- Open access
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YesWhether a free full text is available
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greenOpen access status per OpenAlex
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https://doi.org/10.1101/2025.01.27.635043Direct OA link when available
- Concepts
-
Zebrafish, Regeneration (biology), Axon, Spinal cord injury, Spinal cord, Inflammation, Cell biology, Neuroscience, Biology, Anatomy, Immunology, Gene, BiochemistryTop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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2025: 1Per-year citation counts (last 5 years)
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158Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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| referenced_works_count | 158 |
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| abstract_inverted_index.We | 71 |
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| abstract_inverted_index.by | 21, 140 |
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| abstract_inverted_index.to | 96, 164 |
| abstract_inverted_index.we | 50 |
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| abstract_inverted_index.ONE | 150 |
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| abstract_inverted_index.not | 47 |
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| abstract_inverted_index.state | 79, 92 |
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| abstract_inverted_index.which | 65 |
| abstract_inverted_index.(CNS). | 18 |
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| abstract_inverted_index.matrix | 25 |
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| abstract_inverted_index.system | 17, 41 |
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| abstract_inverted_index.SUMMARY | 152 |
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| abstract_inverted_index.influx, | 108 |
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| cited_by_percentile_year.max | 95 |
| cited_by_percentile_year.min | 91 |
| countries_distinct_count | 0 |
| institutions_distinct_count | 15 |
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| citation_normalized_percentile.is_in_top_10_percent | True |