Biphasic inflammation control by fibroblasts enables spinal cord regeneration in zebrafish

John N, Fleming T, Kolb J, Lyraki O, Vásquez Sepúlveda SI, Parmar A, Kim K, Tarczewska M, Gupta P, Singh K, Marini F, Singh SP, Tsata V, Falk S, Franze K, Guck J, Wehner D (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 44

Pages Range: 116469

Article Number: 116469

Issue: 11

DOI: 10.1016/j.celrep.2025.116469

Abstract

Fibrosis and persistent inflammation are interconnected processes that inhibit axon regeneration in the mammalian central nervous system (CNS). Here, we show that in zebrafish, the interplay between fibroblasts and immune cells is required for regeneration. Using temporally resolved single-cell transcriptomics, we identify a transient, injury-induced cthrc1a+ fibroblast state with an inflammation-associated, less differentiated, non-fibrotic profile. Ca2+-dependent induction of this fibroblast state precedes and is critical for the initiation of the inflammatory response. Subsequently, cthrc1a+ fibroblasts coordinate the resolution of the neutrophil-driven inflammation. Disruption of these inflammation dynamics alters the mechano-structural properties of the lesion microenvironment and inhibits regeneration and recovery of locomotor function. Thus, zebrafish fibroblasts possess a dual role in inducing and resolving inflammation, which are both required for regeneration. This establishes the biphasic inflammation control by fibroblasts as an important mechanism directing CNS regeneration.

Authors with CRIS profile

Nora John
Julia Kolb
Sebastián Ignacio Vásquez Sepúlveda Lehrstuhl für Medizinische Physik und Mikrogewebetechnik Maria Tarczewska Lehrstuhl für Medizinische Physik und Mikrogewebetechnik Pooja Gupta Professur für Stammzell-Modelle seltener neuraler Erkrankungen Sven Falk Lehrstuhl für Biochemie und Pathobiochemie Kristian Franze Lehrstuhl für Medizinische Physik und Mikrogewebetechnik Jochen Guck Lehrstuhl für Biologische Optomechanik

Involved external institutions

Academy of Athens / Ακαδημία Αθηνών GR Greece (GR) Max-Planck-Institut für die Physik des Lichts (MPL) / Max Planck Institute for the Science of Light DE Germany (DE) Université libre de Bruxelles (ULB) / Free University of Brussels BE Belgium (BE) Johannes Gutenberg-Universität Mainz (JGU) DE Germany (DE)

How to cite

APA:

John, N., Fleming, T., Kolb, J., Lyraki, O., Vásquez Sepúlveda, S.I., Parmar, A.,... Wehner, D. (2025). Biphasic inflammation control by fibroblasts enables spinal cord regeneration in zebrafish. Cell Reports, 44, 116469. https://doi.org/10.1016/j.celrep.2025.116469

MLA:

John, Nora, et al. "Biphasic inflammation control by fibroblasts enables spinal cord regeneration in zebrafish." Cell Reports 44 (2025): 116469.

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