[HTML][HTML] Unique and independent roles for MLL in adult hematopoietic stem cells and progenitors

CD Jude, L Climer, D Xu, E Artinger, JK Fisher, P Ernst - Cell stem cell, 2007 - cell.com
CD Jude, L Climer, D Xu, E Artinger, JK Fisher, P Ernst
Cell stem cell, 2007cell.com
Summary The Mixed Lineage Leukemia (MLL) gene is essential for embryonic
hematopoietic stem cell (HSC) development, but its role during adult hematopoiesis is
unknown. Using an inducible knockout model, we demonstrate that Mll is essential for the
maintenance of adult HSCs and progenitors, with fatal bone marrow failure occurring within
3 weeks of Mll deletion. Mll-deficient cells are selectively lost from mixed bone marrow
chimeras, demonstrating their failure to self-renew even in an intact bone marrow …
Summary
The Mixed Lineage Leukemia (MLL) gene is essential for embryonic hematopoietic stem cell (HSC) development, but its role during adult hematopoiesis is unknown. Using an inducible knockout model, we demonstrate that Mll is essential for the maintenance of adult HSCs and progenitors, with fatal bone marrow failure occurring within 3 weeks of Mll deletion. Mll-deficient cells are selectively lost from mixed bone marrow chimeras, demonstrating their failure to self-renew even in an intact bone marrow environment. Surprisingly, HSCs lacking Mll exhibit ectopic cell-cycle entry, resulting in the depletion of quiescent HSCs. In contrast, Mll deletion in myelo-erythroid progenitors results in reduced proliferation and reduced response to cytokine-induced cell-cycle entry. Committed lymphoid and myeloid cells no longer require Mll, defining the early multipotent stages of hematopoiesis as Mll dependent. These studies demonstrate that Mll plays selective and independent roles within the hematopoietic system, maintaining quiescence in HSCs and promoting proliferation in progenitors.
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