期刊
CELL STEM CELL
卷 1, 期 3, 页码 324-337出版社
CELL PRESS
DOI: 10.1016/j.stem.2007.05.019
关键词
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资金
- NCRR NIH HHS [P20 RR016437] Funding Source: Medline
- NHLBI NIH HHS [R01 HL090036, R01 HL090036-01A2] Funding Source: Medline
- NIAID NIH HHS [R01 AI051427] Funding Source: Medline
- NIDDK NIH HHS [K01 DK067119-04, DK067119, K01 DK067119] Funding Source: Medline
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 MY 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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