PUBLICATION
M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands
- Authors
- Hason, M., Mikulasova, T., Machonova, O., Pombinho, A.R., van Ham, T.J., Irion, U., Nüsslein-Volhard, C., Bartunek, P., Svoboda, O.
- ID
- ZDB-PUB-220104-25
- Date
- 2022
- Source
- Blood advances 6(5): 1474-1488 (Journal)
- Registered Authors
- Bartunek, Petr, Irion, Uwe, Machonova, Olga, Nüsslein-Volhard, Christiane, Svoboda, Ondrej, van Ham, Tjakko
- Keywords
- none
- MeSH Terms
-
- Animals
- Carrier Proteins/metabolism
- Hematopoiesis
- Ligands
- Receptor Protein-Tyrosine Kinases/metabolism
- Receptor, Macrophage Colony-Stimulating Factor*/metabolism
- Signal Transduction
- Zebrafish*/genetics
- PubMed
- 34979548 Full text @ Blood Adv
Citation
Hason, M., Mikulasova, T., Machonova, O., Pombinho, A.R., van Ham, T.J., Irion, U., Nüsslein-Volhard, C., Bartunek, P., Svoboda, O. (2022) M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands. Blood advances. 6(5):1474-1488.
Abstract
Macrophage colony-stimulating factor receptor (M-CSFR/CSF1R) signaling is crucial for the differentiation, proliferation, and survival of myeloid cells. The CSF1R pathway is a promising therapeutic target in many human diseases, including neurological disorders or cancer. Zebrafish are commonly used for human disease modeling and preclinical therapeutic screening. Therefore, it is necessary to understand the proper function of cytokine signaling in zebrafish to reliably model human-related diseases. Here, we investigate the roles of zebrafish Csf1rs and their ligands - Csf1a, Csf1b and Il34, in embryonic and adult myelopoiesis. The proliferative effect of exogenous Csf1a on embryonic macrophages is connected to both receptors, Csf1ra and Csf1rb, however there is no evident effect of Csf1b in zebrafish embryonic myelopoiesis. Furthermore, we uncover an unknown role of Csf1rb in zebrafish granulopoiesis. Deregulation of Csf1rb signaling leads to failure in myeloid differentiation resulting in neutropenia throughout the whole lifespan. Surprisingly, Il34 signaling through Csf1rb seems to be of high importance as both csf1rbΔ4bp and il34Δ5bp deficient zebrafish larvae lack granulocytes. Our single-cell RNA sequencing analysis of adult whole kidney marrow (WKM) hematopoietic cells suggests that csf1rb is expressed mainly by blood and myeloid progenitors and that the expression of csf1ra and csf1rb is non-overlapping. We point out differentially expressed genes important in hematopoietic cell differentiation and immune response in selected WKM populations. Our findings could improve the understanding of myeloid cell function and lead to the further study of CSF1R pathway deregulation in disease, mostly in cancerogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping