Oncostatin M and Kit-Ligand Control Hematopoietic Stem Cell Fate during Zebrafish Embryogenesis

Stem Cell Reports
Christopher B MahonyJulien Y Bertrand

Abstract

Understanding the molecular pathways controlling hematopoietic stem cell specification and expansion is a necessary milestone to perform regenerative medicine. Here, we used the zebrafish model to study the role of the ckit signaling pathway in this process. We show the importance of kitb/kitlgb signaling in the specification and expansion of hematopoietic stem cells (HSCs), in the hemogenic endothelium and caudal hematopoietic tissue (CHT), respectively. Moreover, we identified the zebrafish ortholog of Oncostatin M (osm) in the zebrafish genome. We show that the osm/osmr pathway acts upstream of kitb during specification of the hemogenic endothelium, while both pathways act synergistically to expand HSCs in the CHT. Moreover, we found that osm, in addition to its role in promoting HSC proliferation, inhibits HSC commitment to the lymphoid fate. Altogether, our data identified two cytokines, kitlgb and osm, secreted by the vascular niche, that control HSCs during early embryonic development.

Citations

Feb 16, 2019·Growth Factors·Vahid Pazhakh, Graham J Lieschke
Sep 1, 2018·EMBO Reports·Emanuele AzzoniMarella Ftr de Bruijn
Nov 15, 2018·Blood Advances·Samuel J Wattrus, Leonard I Zon
Sep 15, 2019·Disease Models & Mechanisms·Martina KonantzClaudia Lengerke
Jan 9, 2019·Frontiers in Cell and Developmental Biology·Jana OltovaPetr Bartunek
Mar 28, 2019·Frontiers in Cell and Developmental Biology·Christopher B Mahony, Julien Y Bertrand
Dec 8, 2020·Frontiers in Cell and Developmental Biology·Adam M HeckBrandon Hadland
Jan 24, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kristin DietrichFranziska Knopf

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Methods Mentioned

BETA
fluorescence-activated cell sorting
FACS
transgenic
FCS
PCR

Software Mentioned

cellSens Dimension
GraphPad Prism
FlowJo
Excel
EMBOSS Needle

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