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

Autor(es)

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: CELLULAR SIGNALLING; v. 67, MAR 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 15/16799-3 - Investigação do papel do Ca2+ intracelular como modulador da célula-tronco hematopoética e leucêmica
• Beneficiário: Edgar Julian Paredes-Gamero
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 15/24464-1 - Aspectos subcelulares da sinalização de Ca2+ no controle da proliferação da célula-tronco hematopoética por interleucina-3 e pelo fator estimulador de colônias de granulócitos/macrófago
• Beneficiário: Marina Mastelaro de Rezende
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/23787-4 - Sinalização Wnt e de cálcio em células hematopoiéticas tronco normais e leucêmicas
• Beneficiário: Marina Mastelaro de Rezende
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado