[HTML][HTML] Mll has a critical role in fetal and adult hematopoietic stem cell self-renewal

KA McMahon, SYL Hiew, S Hadjur, H Veiga-Fernandes… - Cell stem cell, 2007 - cell.com
KA McMahon, SYL Hiew, S Hadjur, H Veiga-Fernandes, U Menzel, AJ Price, D Kioussis…
Cell stem cell, 2007cell.com
Summary The Mixed Lineage Leukemia (Mll) gene is a homolog of Drosophila Trithorax
commonly rearranged in infant leukemia. Comprehensive analysis of the role of Mll in
hematopoiesis in fetal and adult knockout mice has been prevented by the lethality of Mll−/−
mice. We have established a conditional deletion model that allows us to study adult
hematopoiesis in the absence of Mll. In this study, Mll−/− embryos survive to E16. 5 and
have reduced numbers of HSCs. The quiescent fraction of these HSCs is greatly reduced …
Summary
The Mixed Lineage Leukemia (Mll) gene is a homolog of Drosophila Trithorax commonly rearranged in infant leukemia. Comprehensive analysis of the role of Mll in hematopoiesis in fetal and adult knockout mice has been prevented by the lethality of Mll−/− mice. We have established a conditional deletion model that allows us to study adult hematopoiesis in the absence of Mll. In this study, Mll−/− embryos survive to E16.5 and have reduced numbers of HSCs. The quiescent fraction of these HSCs is greatly reduced, and they are unable to compete with wild-type cells in transplantation assays. Mice with Mll expression conditionally deleted in the hematopoietic system have grossly normal hematopoiesis in bone marrow, thymus, and spleen. However, transplanted Mll-deficient bone marrow cells are highly compromised in their ability to competitively reconstitute irradiated recipients. These results suggest a critical role for Mll in regulating stem cell self-renewal.
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