The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages

The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages
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DOI:
10.1016/s0092-8674(00)80076-8
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发表时间:
1996-07-12
期刊:
影响因子:
64.5
通讯作者:
Orkin, SH
Orkin, SH
中科院分区:
生物学1区
文献类型:
--
作者:
Porcher, C;Swat, W;Orkin, SH

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T细胞白血病癌蛋白SCL/tal-1是一种碱性-螺旋-环-螺旋转录因子,是小鼠卵黄囊中胚胎红细胞产生所必需的。为了确定在其他谱系中的作用,我们研究了纯合突变SCL/tal-1 -/-胚胎干细胞在体外分化和嵌合小鼠体内的造血潜能。在这里,我们表明,在SCL/tal-1的情况下,造血,包括红细胞,骨髓细胞,巨核细胞,肥大细胞,T和B淋巴细胞的产生,是不可检测的。这些研究结果表明,SCL/tal-1功能非常早的造血发育,无论是在规范腹侧中胚层的血细胞的命运,或在形成或维持未成熟的祖细胞。
The T cell leukemia oncoprotein SCL/tal-1, a basic-helix-loop-helix transcription factor, is required for production of embryonic red blood cells in the mouse yolk sac. To define roles in other lineages, we studied the hematopoietic potential of homozygous mutant SCL/tal-1 -/- embryonic stem cells upon in vitro differentiation and in vivo in chimeric mice. Here we show that in the absence of SCL/tal-1, hematopoiesis, including the generation of red cells, myeloid cells, megakaryocytes, mast cells, and both T and B lymphoid cells, is undetectable. These findings suggest that SCL/tal-1 functions very early in hematopoietic development, either in specification of ventral mesoderm to a blood cell fate, or in formation or maintenance of immature progenitors.