PUBLICATION
Zebrafish Kit ligands cooperate with erythropoietin to promote erythroid cell expansion
- Authors
- Oltova, J., Svoboda, O., Machonova, O., Svatonova, P., Traver, D., Kolar, M., Bartunek, P.
- ID
- ZDB-PUB-201202-19
- Date
- 2020
- Source
- Blood advances 4: 5915-5924 (Journal)
- Registered Authors
- Bartunek, Petr, Machonova, Olga, Oltova, Jana, Svoboda, Ondrej, Traver, David
- Keywords
- none
- MeSH Terms
-
- Animals
- Erythroid Cells
- Erythropoietin*
- Ligands
- Stem Cell Factor*/genetics
- Zebrafish
- PubMed
- 33259600 Full text @ Blood Adv
Citation
Oltova, J., Svoboda, O., Machonova, O., Svatonova, P., Traver, D., Kolar, M., Bartunek, P. (2020) Zebrafish Kit ligands cooperate with erythropoietin to promote erythroid cell expansion. Blood advances. 4:5915-5924.
Abstract
Kit ligand (Kitlg) is pleiotropic cytokine with a prominent role in vertebrate erythropoiesis. Although the role of Kitlg in this process has not been reported in Danio rerio (zebrafish), in the present study we show that its function is evolutionarily conserved. Zebrafish possess 2 copies of Kitlg genes (Kitlga and Kitlgb) as a result of whole-genome duplication. To determine the role of each ligand in zebrafish, we performed a series of ex vivo and in vivo gain- and loss-of-function experiments. First, we tested the biological activity of recombinant Kitlg proteins in suspension culture from zebrafish whole-kidney marrow, and we demonstrate that Kitlga is necessary for expansion of erythroid progenitors ex vivo. To further address the role of kitlga and kitlgb in hematopoietic development in vivo, we performed gain-of-function experiments in zebrafish embryos, showing that both ligands cooperate with erythropoietin (Epo) to promote erythroid cell expansion. Finally, using the kita mutant (kitab5/b5 or sparse), we show that the Kita receptor is crucial for Kitlga/b cooperation with Epo in erythroid cells. In summary, using optimized suspension culture conditions with recombinant cytokines (Epo, Kitlga), we report, for the first time, ex vivo suspension cultures of zebrafish hematopoietic progenitor cells that can serve as an indispensable tool to study normal and aberrant hematopoiesis in zebrafish. Furthermore, we conclude that, although partial functional diversification of Kit ligands has been described in other processes, in erythroid development, both paralogs play a similar role, and their function is evolutionarily conserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping