Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells
Monocytic leukemia zinc finger protein is essential for the development of long-term reconstituting hematopoietic stem cells
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DOI：
10.1101/gad.1382606
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发表时间：
2006-05-01
影响因子：
10.5
通讯作者：
Voss, AK
中科院分区：
文献类型：
--
作者：
Thomas, T;Corcoran, LM;Voss, AK
单核细胞白血病锌指蛋白（MOZ）是一种转录共激活因子，属于组蛋白乙酰转移酶MYST家族，是急性髓系白血病复发性易位的靶点。由于与白血病易位相关的基因通常是血液形成的重要调节因子，我们研究了Moz是否在正常造血中发挥作用。我们制造了携带Moz基因突变的小鼠。纯合子Moz突变小鼠在出生时死亡。Moz突变胎肝造血细胞移植后不能为受体造血系统提供造血功能。我们观察到Moz-deficient小鼠的干细胞区室中存在严重缺陷。所有血统的祖先数量减少。然而，血细胞谱系定型不受影响。总之，这些结果表明，Moz对于造血干细胞的基本性质，移植后重建受体造血系统的能力是必不可少的，并且Moz在干细胞区室中是特别需要的。
Monocytic leukemia zinc finger protein (MOZ), a transcriptional coactivator and member of the MYST family of histone acetyltransferases, is the target of recurrent translocations in acute myeloid leukemia. Since genes associated with translocations in leukemia are typically important regulators of blood formation, we investigated if Moz has a role in normal hematopoiesis. We generated mice carrying a mutation in the Moz gene. Homozygous Moz mutant mice died at birth. Moz mutant fetal liver hematopoietic cells were incapable of contributing to the hematopoietic system of recipients after transplantation. We observed profound defects in the stem cell compartment of Moz-deficient mice. Progenitors of all lineages were reduced in number. However, blood cell lineage commitment was unaffected. Together, these results show that Moz is essential for a fundamental property of hematopoietic stem cells, the ability to reconstitute the hematopoietic system of a recipient after transplantation and that Moz is specifically required in the stem cell compartment.