Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells
Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells
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DOI：
10.1126/science.1106114
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发表时间：
2005-02-18
期刊：
影响因子：
56.9
通讯作者：
Korsmeyer, SJ
中科院分区：
文献类型：
--
作者：
Opferman, JT;Iwasaki, H;Korsmeyer, SJ
细胞凋亡是控制造血干细胞(HSC)数量的重要因素。然而，调控HSC动态平衡的特定bcl2家族成员(S)还没有得到准确的定义。我们测试了髓系白血病-1(MCL-1)作为一个有吸引力的候选细胞，它在造血干细胞中高表达，并受到生长因子信号的调节。在小鼠中诱导Mcl-1的缺失导致了骨髓的消融。这导致了早期骨髓祖细胞群体的丧失，包括造血干细胞。此外，包括干细胞因子在内的生长因子增加了Mcl-1基因的转录，并需要MCL-1来增强纯化的骨髓前体细胞的存活。Mcl-1在包括肝脏在内的其他组织中的缺失不会影响患者的存活率。因此，MCL-1是确保早期造血祖细胞内环境稳定所必需的关键和特异的调节因子。
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.