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| [PMID]: | 27988259 |
| [Au] Autor: | Nguyen TM; Arthur A; Zannettino AC; Gronthos S |
| [Ad] Endereço: | Mesenchymal Stem Cell Laboratory, Adelaide Medical School, Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, Australia; Cancer Theme, South Australian Health and Medical Research Institute, Adelaide, SA, Australia. |
| [Ti] Título: | EphA5 and EphA7 forward signaling enhances human hematopoietic stem and progenitor cell maintenance, migration, and adhesion via Rac1 activation. |
| [So] Source: | Exp Hematol;48:72-78, 2017 Apr. | | [Is] ISSN: | 1873-2399 |
| [Cp] País de publicação: | Netherlands |
| [La] Idioma: | eng |
| [Ab] Resumo: | The proliferation, differentiation, adhesion, and migration of hematopoietic stem and progenitor cells (HSPCs) are dependent upon bone marrow stromal cells (BMSCs). In this study, we found that human primitive HSPCs (CD34 CD38 ), but not lineage-committed hematopoietic cell populations, express the tyrosine kinase receptors EphA5 and EphA7. Moreover, we found that the ephrinA5 ligand, the high-affinity binding partner of EphA5 and EphA7, is highly expressed by primary human BMSCs. Previous studies have reported that interactions between EphA and ephrinA play important roles in hematopoietic cell trafficking; however, their role in BMSC support of hematopoiesis had not been described previously. Herein, we show that stimulating EphA5 and/or EphA7 forward signaling in HSPCs using soluble ephrinA5-Fc molecules promoted human HSPC-derived colony formation significantly and was associated with increased expression of granulocyte macrophage colony-stimulating factor receptor on HSPCs. Studies using functional blocking peptides to EphA5/7 found that disruption of EphA5/ephrinA5 and/or EphA7/ephrinA5 interactions inhibited HSPC function in BMSC-dependent long-term culture-initiating cell assays. Furthermore, the adhesion and migration of HSPCs was increased significantly in the presence of ephrinA5-Fc molecules compared with human immunoglobulin G-treated controls. Conversely, blocking EphA5 activation led to a reduction of HSPC adhesion, whereas inhibiting EphA5 and/or EphA7 activation hindered HSPC migration. Analysis of HSPC cultured in the presence of ephrinA5-Fc showed that EphA forward signaling stimulated Rac1 gene and protein expression and the Rac1 target molecule WAVE1. Moreover, a significant reduction of ephrinA5-mediated HSPC adhesion and migration was observed in the presence of Rac1 inhibitor. These findings suggest that interactions between EphA and ephrinA5 are important in maintaining the HSPC niche mediated in part by activation of Rac1 signaling. |
| [Mh] Termos MeSH primário: |
Movimento Celular
Autorrenovação Celular
Células-Tronco Hematopoéticas/citologia
Células-Tronco Hematopoéticas/fisiologia
Receptor EphA5/metabolismo
Receptor EphA7/metabolismo
Transdução de Sinais
Proteínas rac1 de Ligação ao GTP/metabolismo
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| [Mh] Termos MeSH secundário: |
Adesão Celular/genética
Comunicação Celular
Diferenciação Celular
Movimento Celular/genética
Autorrenovação Celular/genética
Perfilação da Expressão Gênica
Seres Humanos
Receptor EphA5/genética
Receptor EphA7/genética
Células-Tronco
Células Estromais/metabolismo
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| EC 2.7.10.1 (Receptor, EphA5); EC 2.7.10.1 (Receptor, EphA7); EC 3.6.5.2 (rac1 GTP-Binding Protein) |
| [Em] Mês de entrada: | 1706 |
| [Cu] Atualização por classe: | 170606 |
[Lr] Data última revisão:
| 170606 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 161219 |
| [St] Status: | MEDLINE |
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