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Hoxb4-YFP reporter mouse model: a novel tool for tracking HSC development and studying the role of Hoxb4 in hematopoiesis.

TitleHoxb4-YFP reporter mouse model: a novel tool for tracking HSC development and studying the role of Hoxb4 in hematopoiesis.
Publication TypeJournal Article
Year of Publication2011
AuthorsHills D, Gribi R, Ure J, Buza-Vidas N, Luc S, Jacobsen SEirik W, Medvinsky AL
Date Published2011 Mar 31
KeywordsAnimals, Bacterial Proteins, Cell Tracking, Embryo, Mammalian, Female, Genes, Reporter, Hematopoiesis, Hematopoietic Stem Cells, Homeodomain Proteins, Luminescent Proteins, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Models, Animal, Models, Biological, Pregnancy, Recombinant Fusion Proteins, Transcription Factors

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.

Alternate JournalBlood
PubMed ID21278354
Grant ListG0501838 / / Medical Research Council / United Kingdom
G0801073 / / Medical Research Council / United Kingdom
G0900962 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom