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Publication : Definitive hematopoiesis requires the mixed-lineage leukemia gene.

First Author  Ernst P Year  2004
Journal  Dev Cell Volume  6
Issue  3 Pages  437-43
PubMed ID  15030765 Mgi Jnum  J:147266
Mgi Id  MGI:3839820 Doi  10.1016/s1534-5807(04)00061-9
Citation  Ernst P, et al. (2004) Definitive hematopoiesis requires the mixed-lineage leukemia gene. Dev Cell 6(3):437-43
abstractText  The Mixed-Lineage Leukemia (MLL) gene encodes a Trithorax-related chromatin-modifying protooncogene that positively regulates Hox genes. In addition to their well-characterized roles in axial patterning, Trithorax and Polycomb family proteins perform less-understood functions in vertebrate hematopoiesis. To define the role of MLL in the development of the hematopoietic system, we examined the potential of cells lacking MLL. Mll-deficient cells could not develop into lymphocytes in adult RAG-2 chimeric animals. Similarly, in vitro differentiation of B cells required MLL. In chimeric embryos, Mll-deficient cells failed to contribute to fetal liver hematopoietic stem cell/progenitor populations. Moreover, we show that aorta-gonad-mesonephros (AGM) cells from Mll-deficient embryos lacked hematopoietic stem cell (HSC) activity despite their ability to generate hematopoietic progeny in vitro. These results demonstrate an intrinsic requirement for MLL in definitive hematopoiesis, where it is essential for the generation of HSCs in the embryo.
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