Common and specific gene regulatory programs in zebrafish caudal fin regeneration at single-cell resolution
- Yujie Chen1,2,3,7,
- Yiran Hou1,2,3,7,8,
- Qinglin Zeng1,2,3,
- Irene Wang1,2,
- Meiru Shang1,2,
- Kwangdeok Shin4,
- Christopher Hemauer1,2,9,
- Xiaoyun Xing1,2,3,
- Junsu Kang4,
- Guoyan Zhao1,5,6 and
- Ting Wang1,2,3
- 1Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA;
- 2The Edison Family Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA;
- 3McDonnell Genome Institute, Washington University School of Medicine, St. Louis, Missouri, USA;
- 4Department of Cell and Regenerative Biology, School of Medicine and Public Health, University of Wisconsin Madison, Madison, Wisconsin 53705, USA;
- 5Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA;
- 6Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA
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↵7 These authors contributed equally to this work.
Abstract
Following amputation, zebrafish regenerate their injured caudal fin through lineage-restricted reprogramming. Although previous studies have charted various genetic and epigenetic dimensions of this process, the intricate gene regulatory programs shared by, or unique to, different regenerating cell types remain underinvestigated. Here, we mapped the regulatory landscape of fin regeneration by applying paired snRNA-seq and snATAC-seq on uninjured and regenerating fins. This map delineates the regulatory dynamics of predominant cell populations at multiple stages of regeneration. We observe a marked increase in the accessibility of chromatin regions associated with regenerative and developmental processes at 1 dpa, followed by a gradual closure across major cell types at later stages. This pattern is distinct from that of transcriptomic dynamics, which is characterized by several waves of gene upregulation and downregulation. We identified and in vivo validated cell-type-specific and position-specific regeneration-responsive enhancers and constructed regulatory networks by cell type and stage. Our single-cell resolution transcriptomic and chromatin accessibility map across regenerative stages provides new insights into regeneration regulatory mechanisms and serves as a valuable resource for the community.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.279372.124.
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Freely available online through the Genome Research Open Access option.
- Received March 18, 2024.
- Accepted November 4, 2024.
This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
