ArticleBlood advances2021
A zebrafish model of granulin deficiency reveals essential roles in myeloid cell differentiation.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 24 citations in OpenAlex.
- Synergistic cooperation between progranulin and Jak2/Stat3 signaling determines definitive myeloid cell fate.Cell reports · 2026Article
- Regenerative macrophages enhance stem cell-derived β cell function and engraftment.Science advances · 2026Article
- Immune-Enhancing Effects ofCurrent issues in molecular biology · 2026Article
- Immune modulation promotes heart regeneration through macrophage and Granulin functions in medaka.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Progranulin's Protective Mechanisms and Therapeutic Potential in Cardiovascular Disease.Cells · 2025Review
- Common and specific gene regulatory programs in zebrafish caudal fin regeneration at single-cell resolution.Genome research · 2025Article
- Single-cell analysis of microglial activation after traumatic brain injury reveals immune signaling pathways linked to mitochondrial dysfunction and brain aging.Frontiers in aging neuroscience · 2025Article
- p65 signaling dynamics drive the developmental progression of hematopoietic stem and progenitor cells through cell cycle regulation.Nature communications · 2024Article
- Zebrafish as a Model Organism for Studying Pathologic Mechanisms of Neurodegenerative Diseases and other Neural Disorders.Cellular and molecular neurobiology · 2023Review
- mCell proliferation · 2023Article
- Zebrafish: A Relevant Genetic Model for Human Primary Immunodeficiency (PID) Disorders?International journal of molecular sciences · 2023Review
- Zebrafish: a convenient tool for myelopoiesis research.Cell regeneration (London, England) · 2023Review
- Identification of Transcription Factor Binding Sites by Cleavage Under Target and Release Using Nuclease in Zebrafish.Zebrafish · 2022Article
- Identification of chromatin states during zebrafish gastrulation using CUT&RUN and CUT&Tag.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Article
- Epigenetic Regulation of Endothelial Cell Lineages During Zebrafish Development-New Insights From Technical Advances.Frontiers in cell and developmental biology · 2022Review
- Dietary Inclusion of Seabuckthorn (Frontiers in physiology · 2022Article
- Thymus-Derived CD4Journal of immunology (Baltimore, Md. : 1950) · 2021Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Granulin is a pleiotropic protein involved in inflammation, wound healing, neurodegenerative disease, and tumorigenesis. These roles in human health have prompted research efforts to use granulin to treat rheumatoid arthritis and frontotemporal dementia and to enhance wound healing. But how granulin contributes to each of these diverse biological functions remains largely unknown. Here, we have uncovered a new role for granulin during myeloid cell differentiation. We have taken advantage of the tissue-specific segregation of the zebrafish granulin paralogues to assess the functional role of granulin in hematopoiesis without perturbing other tissues. By using our zebrafish model of granulin deficiency, we revealed that during normal and emergency myelopoiesis, myeloid progenitors are unable to terminally differentiate into neutrophils and macrophages in the absence of granulin a (grna), failing to express the myeloid-specific genes cebpa, rgs2, lyz, mpx, mpeg1, mfap4, and apoeb. Functionally, macrophages fail to recruit to the wound, resulting in abnormal healing. Our CUT&RUN experiments identify Pu.1, which together with Irf8, positively regulates grna expression. In vivo imaging and RNA sequencing experiments show that grna inhibits the expression of gata1, leading to the repression of the erythroid program. Importantly, we demonstrated functional conservation between the mammalian granulin and the zebrafish ortholog grna. Our findings uncover a previously unrecognized role for granulin during myeloid cell differentiation, which opens a new field of study that can potentially have an impact on different aspects of human health and expand the therapeutic options for treating myeloid disorders such as neutropenia or myeloid leukemia.
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