Zebrafish Kit ligands cooperate with erythropoietin to promote erythroid cell expansion

0539675 - ÚMG 2021 RIV US eng J - Journal Article
Oltová, Jana - Svoboda, Ondřej - Machoňová, Olga - Svatoňová, Petra - Traver, D. - Kolář, Michal - Bartůněk, Petr
Zebrafish Kit ligands cooperate with erythropoietin to promote erythroid cell expansion.
Blood Advances. Roč. 4, č. 23 (2020), s. 5915-5924. ISSN 2473-9529. E-ISSN 2473-9537
R&D Projects: GA ČR GA16-21024S; GA MZd NV19-07-00412
Institutional support: RVO:68378050
Keywords : c-kit * progenitor cells * terminal differentiation * glucocorticoid-receptor * clonal analysis * growth-factor * gene-product * hematopoiesis * expression * chicken
OECD category: Cell biology
Impact factor: 6.799, year: 2020
Method of publishing: Open access
https://ashpublications.org/bloodadvances/article/4/23/5915/474371/Zebrafish-Kit-ligands-cooperate-with

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 (kita(b5/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.
Permanent Link: http://hdl.handle.net/11104/0317388