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Hoxb4-YFP reporter mouse model: a novel tool for tracking HSC development and studying the role of Hoxb4 in hematopoiesis.
Hills, David; Gribi, Ruby; Ure, Jan; Buza-Vidas, Natalija; Luc, Sidinh; Jacobsen, Sten Eirik W; Medvinsky, Alexander.
Afiliação
  • Hills D; Ontogeny of Haematopoietic Stem Cells Group, Medical Research Council/Juvenile Diabetes Research Foundation Centre for Development in Stem Cell Biology, Institute for Stem Cell Research, University of Edinburgh, West Mains Road, Edinburgh, United Kingdom.
Blood ; 117(13): 3521-8, 2011 Mar 31.
Article em En | MEDLINE | ID: mdl-21278354
Hoxb4 overexpression promotes dramatic expansion of bone marrow (BM) hematopoietic stem cells (HSCs) without leukemic transformation and induces development of definitive HSCs from early embryonic yolk sac and differentiating embryonic stem cells. Knockout studies of Hoxb4 showed little effect on hematopoiesis, but interpretation of these results is obscured by the lack of direct evidence that Hoxb4 is expressed in HSCs and possible compensatory effects of other (Hox) genes. To evaluate accurately the pattern of Hoxb4 expression and to gain a better understanding of the physiologic role of Hoxb4 in the hemato-poietic system, we generated a knock-in Hoxb4-yellow fluorescent protein (YFP) reporter mouse model. We show that BM Lin(-)Sca1(+)c-Kit(+) cells express Hoxb4-YFP and demonstrate functionally in the long-term repopulation assay that definitive HSCs express Hoxb4. Similarly, aorta-gonad-mesonephrous-derived CD45(+)CD144(+) cells, enriched for HSCs, express Hoxb4. Furthermore, yolk sac and placental HSC populations express Hoxb4. Unexpectedly, Hoxb4 expression in the fetal liver HSCs is lower than in the BM, reaching negligible levels in some HSCs, suggesting an insignificant role of Hoxb4 in expansion of fetal liver HSCs. Hoxb4 expression therefore would not appear to correlate with the cycling status of fetal liver HSCs, although highly proliferative HSCs from young BM show strong Hoxb4 expression.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Fatores de Transcrição / Células-Tronco Hematopoéticas / Genes Reporter / Proteínas de Homeodomínio / Rastreamento de Células / Hematopoese / Proteínas Luminescentes Tipo de estudo: Prognostic_studies Limite: Animals / Pregnancy Idioma: En Revista: Blood Ano de publicação: 2011 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Bactérias / Fatores de Transcrição / Células-Tronco Hematopoéticas / Genes Reporter / Proteínas de Homeodomínio / Rastreamento de Células / Hematopoese / Proteínas Luminescentes Tipo de estudo: Prognostic_studies Limite: Animals / Pregnancy Idioma: En Revista: Blood Ano de publicação: 2011 Tipo de documento: Article