Divergent effects of Wnt5b on IL-3-and GM-CSF-induced myeloid differentiation

Author(s)

de Rezende, Marina Mastelaro ^{[1, 2]} ; Ng-Blichfeldt, John-Poul ^{[2, 3]} ; Justo, Giselle Zenker ^{[1, 4]} ; Paredes-Gamero, Edgar Julian ^{[1, 5]} ; Gosens, Reinoud ^[2]

Affiliation

^[1] Univ Fed Sao Paulo UNIFESP, Dept Bioquim, BR-04044020 Sao Paulo - Brazil

^[2] Univ Groningen, Dept Mol Pharmacol, NL-9713 AV Groningen - Netherlands

^[3] Cambridge Biomed Campus, MRC Lab Mol Biol, Cambridge CB2 0QH - England

^[4] Univ Fed Sao Paulo UNIFESP, Dept Ciencias Farmaceut, BR-09913030 Diadema - Brazil

^[5] Univ Fed Mato Grosso do Sul, Fac Ciencias Farmaceut Alimentos & Nutr, BR-79070900 Campo Grande, MS - Brazil

• Document type: Journal article
• Source: CELLULAR SIGNALLING; v. 67, MAR 2020.
• Web of Science Citations: 0

Abstract

The multiple specialized cell types of the hematopoietic system originate from differentiation of hematopoietic stem cells and progenitors (HSPC), which can generate both lymphoid and myeloid lineages. The myeloid lineage is preferentially maintained during ageing, but the mechanisms that contribute to this process are incompletely understood. Here, we studied the roles of Wnt5a and Wnt5b, ligands that have previously been linked to hematopoietic stem cell ageing and that are abundantly expressed by both hematopoietic progenitors and bone-marrow derived niche cells. Whereas Wnt5a had no major effects on primitive cell differentiation, Wnt5b had profound and divergent effects on cytokine-induced myeloid differentiation. Remarkably, while IL-3-mediated myeloid differentiation was largely repressed by Wnt5b, GM-CSF-induced myeloid differentiation was augmented. Furthermore, in the presence of IL-3, Wnt5b enhanced HSPC self-renewal, whereas in the presence of GM-CSF, Wnt5b accelerated differentiation, leading to progenitor cell exhaustion. Our results highlight discrepancies between IL-3 and GM-CSF, and reveal novel effects of Wnt5b on the hematopoietic system. (AU)

• FAPESP's process: 15/16799-3 - Investigating the role of intracellular Ca2+ as a modulator of leukemic and hematopoietic stem cells
• Grantee: Edgar Julian Paredes-Gamero
• Support Opportunities: Regular Research Grants
• FAPESP's process: 15/24464-1 - Subcellular Ca2+ signaling aspects in proliferation control of haemopoietic stem cells by interleukin-3 and granulocyte/macrophage colony stimulating factor
• Grantee: Marina Mastelaro de Rezende
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/23787-4 - Wnt and Ca2+ signaling in normal and leukemic hematopoietic stem cell fate
• Grantee: Marina Mastelaro de Rezende
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate