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Publication : Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells.

First Author  Opferman JT Year  2005
Journal  Science Volume  307
Issue  5712 Pages  1101-4
PubMed ID  15718471 Mgi Jnum  J:96127
Mgi Id  MGI:3529428 Doi  10.1126/science.1106114
Citation  Opferman JT, et al. (2005) Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science 307(5712):1101-4
abstractText  Apoptosis is important in controlling hematopoietic stem cell (HSC) numbers. However, the specific BCL-2 family member(s) that regulate HSC homeostasis are not precisely defined. We tested myeloid leukemia-1 (MCL-1) as an attractive candidate that is highly expressed in HSCs and regulated by growth factor signals. Inducible deletion of Mcl-1 in mice resulted in ablation of bone marrow. This resulted in the loss of early bone marrow progenitor populations, including HSCs. Moreover, growth factors including stem cell factor increased transcription of the Mcl-1 gene and required MCL-1 to augment survival of purified bone marrow progenitors. Deletion of Mcl-1 in other tissues, including liver, did not impair survival. Thus, MCL-1 is a critical and specific regulator essential for ensuring the homeostasis of early hematopoietic progenitors.
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