GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos

GDF3, a BMP inhibitor, regulates cell fate in stem cells and early embryos
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DOI:
10.1242/dev.02192
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发表时间:
2006-01-01
期刊:
影响因子:
4.6
通讯作者:
Brivanlou, AH
Brivanlou, AH
中科院分区:
生物学2区
文献类型:
--
作者:
Levine, AJ;Brivanlou, AH

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TGF β配体超家族在发育和疾病中起着关键作用。在人和小鼠胚胎干细胞中,该家族的成员GDF 3以多能状态特异性表达。我们表明,GDF3是一种抑制剂,它自己的亚家族,在多种情况下阻断经典的BMP信号,与BMP蛋白相互作用,并在原肠胚形成过程中的模式与BMP抑制一致的节点中特异性表达。此外,我们使用功能获得和功能减少来表明,GDF 3以物种特异性的方式调节胚胎干细胞的两个主要特征:维持未分化状态的能力和分化成全谱细胞类型的能力。
The TGF beta superfamily of ligands plays key functions in development and disease. in both human and mouse embryonic stem cells, a member of this family, GDF3, is specifically expressed in the pluripotent state. We show that GDF3 is an inhibitor of its own subfamily, blocks classic BMP signaling in multiple contexts, interacts with BMP proteins and is expressed specifically in the node during gastrulation in a pattern consistent with BMP inhibition. Furthermore, we use gain- and reduction-of-function to show that in a species-specific manner, GDF3 regulates both of the two major characteristics of embryonic stem cells: the ability to maintain the undifferentiated state and the ability to differentiate into the full spectrum of cell types.