Mll has a critical role in fetal and adult hematopoietic stem cell self-renewal.
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.
McMahon
Kathryn A
KA
Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, London, WC1N 1EH, UK.
Hiew
Samantha Y-L
SY
Hadjur
Suzana
S
Veiga-Fernandes
Henrique
H
Menzel
Ursula
U
Price
Amanda J
AJ
Kioussis
Dimitris
D
Williams
Owen
O
Brady
Hugh J M
HJ
D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D005333:Fetus / Q000166:cytology* / Q000378:metabolism*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006706:Homeostasis; D008099:Liver / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D051788:Myeloid-Lymphoid Leukemia Protein / Q000172:deficiency / Q000378:metabolism*
D051788:Myeloid-Lymphoid Leukemia Protein