M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F22%3A00558018" target="_blank" >RIV/68378050:_____/22:00558018 - isvavai.cz</a>
Result on the web
<a href="https://ashpublications.org/bloodadvances/article/6/5/1474/483305/M-CSFR-CSF1R-signaling-regulates-myeloid-fates-in" target="_blank" >https://ashpublications.org/bloodadvances/article/6/5/1474/483305/M-CSFR-CSF1R-signaling-regulates-myeloid-fates-in</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1182/bloodadvances.2021005459" target="_blank" >10.1182/bloodadvances.2021005459</a>
Alternative languages
Result language
angličtina
Original language name
M-CSFR/CSF1R signaling regulates myeloid fates in zebrafish via distinct action of its receptors and ligands
Original language description
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 and 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 csf1rb(Delta 4bP)-deficient and il34(Delta 5bp)-deficientzebrafish 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 the expression of csf1ra and csf1rb is nonoverlapping. 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30205 - Hematology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Blood Advances
ISSN
2473-9529
e-ISSN
2473-9537
Volume of the periodical
6
Issue of the periodical within the volume
5
Country of publishing house
US - UNITED STATES
Number of pages
15
Pages from-to
1474-1488
UT code for WoS article
000797026400010
EID of the result in the Scopus database
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