AML1/Runx1 negatively regulates quiescent hematopoietic stem cells in adult hematopoiesis
AML1/Runx1 negatively regulates quiescent hematopoietic stem cells in adult hematopoiesis
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DOI：
10.4049/jimmunol.180.7.4402
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发表时间：
2008-04-01
影响因子：
4.4
通讯作者：
Kurokawa, Mineo
中科院分区：
文献类型：
--
作者：
Ichikawa, Motoshi;Goyama, Susumu;Kurokawa, Mineo
转录因子AML 1/Runx 1最初从人类白血病的t（8;21）染色体易位中分离出来，是小鼠胚胎多系造血发育所必需的。AML 1负调节成人造血中未成熟造血细胞的数量，而它是巨核细胞成熟和淋巴细胞发育所必需的。然而，它仍然有待确定如何AML 1有助于造血干细胞（HSC）的稳态。为了解决这个问题，我们详细分析了AML 1缺失时HSC的功能。值得注意的是，Hoechst 33342侧群部分中的细胞在AML 1缺陷型骨髓中的数量增加，这表明静止HSC的富集。我们还使用有限稀释骨髓移植试验发现，AML 1缺陷骨髓中的HSC数量增加。这些结果表明，静止HSC的数量由AML 1负调控。
Transcription factor AML1/Runx1, initially isolated from the t(8;21) chromosomal translocation in human leukemia, is essential for the development of multilineage hematopoiesis in mouse embryos. AML1 negatively regulates the number of immature hematopoietic cells in adult hematopoiesis, whereas it is required for megakaryocytic maturation and lymphocytic development. However, it remains yet to be determined how AML1 contributes to homeostasis of hematopoietic stem cells (HSCs). To address this issue, we analyzed in detail HSC function in the absence of AML1. Notably, cells in the Hoechst 33342 side population fraction are increased in number in AML1-deficient bone marrow, which suggests enrichment of quiescent HSCs. We also found an increase in HSC number within the AML1-deficient bone marrow using limiting dilution bone marrow transplantation assays. These results indicate that the number of quiescent HSCs is negatively regulated by AML1.