AF10 plays a key role in the survival of uncommitted hematopoietic cells.

AF10 plays a key role in the survival of uncommitted hematopoietic cells.
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DOI:
10.1371/journal.pone.0051626
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Arredondo JJ
Arredondo JJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chamorro-Garcia R;Cervera M;Arredondo JJ

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造血是一个复杂的过程,受细胞内外因素的共同调控。造血过程中关键基因表达的改变可以改变干细胞分化和增殖之间的平衡,并可能最终导致白血病和其他疾病。AF10是一种转录因子,在AF10基因与至少两种其他基因MLL和CALM之一之间的染色体重排后,与白血病的发展有关。AF10和白血病之间的联系,以及已知的AF10和造血调节因子之间的相互作用,表明AF10可能是重要的造血和白血病转化。在这里,我们表明,AF10是重要的适当造血分化。在人造血细胞系和鼠总骨髓细胞中诱导造血分化触发了AF 10 mRNA和蛋白水平的降低,特别是在干细胞和多能祖细胞中。功能获得和丧失研究表明,AF10的过度表达或表达不足导致干细胞和多能祖细胞的凋亡性细胞死亡。我们的结论是,AF 10在维持多能造血细胞中起着关键作用。
Hematopoiesis is a complex process regulated by both cell intrinsic and cell extrinsic factors. Alterations in the expression of critical genes during hematopoiesis can modify the balance between stem cell differentiation and proliferation, and may ultimately give rise to leukemia and other diseases. AF10 is a transcription factor that has been implicated in the development of leukemia following chromosomal rearrangements between the AF10 gene and one of at least two other genes, MLL and CALM. The link between AF10 and leukemia, together with the known interactions between AF10 and hematopoietic regulators, suggests that AF10 may be important in hematopoiesis and in leukemic transformation. Here we show that AF10 is important for proper hematopoietic differentiation. The induction of hematopoietic differentiation in both human hematopoietic cell lines and murine total bone marrow cells triggers a decrease of AF10 mRNA and protein levels, particularly in stem cells and multipotent progenitors. Gain- and loss-of-function studies demonstrate that over- or under-expression of AF10 leads to apoptotic cell death in stem cells and multipotent progenitors. We conclude that AF10 plays a key role in the maintenance of multipotent hematopoietic cells.
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