Hypoxia requires Notch signaling to maintain the undifferentiated cell state

被引：1097

作者：

Gustafsson, MV ^{[1
]}

Zheng, XW ^{[1
]}

Pereira, T ^{[1
]}

Gradin, K ^{[1
]}

Jin, SB ^{[1
]}

Lundkvist, J ^{[1
]}

Ruas, JL ^{[1
]}

Poellinger, L ^{[1
]}

Lendahl, U ^{[1
]}

Bondesson, M ^{[1
]}

机构：

[1] Karolinska Inst, Med Noble Inst, Dept Cell & Mol Biol, SE-17177 Stockholm, Sweden

来源：

DEVELOPMENTAL CELL | 2005年 / 9卷 / 05期

基金：

瑞典研究理事会;

关键词：

D O I：

10.1016/j.devcel.2005.09.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 [细胞生物学]; 090102 [作物遗传育种];

摘要：

In addition to controlling a switch to glycolytic metabolism and induction of erythropoiesis and angiogenesis, hypoxia promotes the undifferentiated cell state in various stem and precursor cell populations. Here, we show that the latter process requires Notch signaling. Hypoxia blocks neuronal and myogenic differentiation in a Notch-dependent manner. Hypoxia activates Notch-responsive promoters and increases expression of Notch direct downstream genes. The Notch intracellular domain interacts with HIF-1 alpha, a global regulator of oxygen homeostasis, and HIF-1a is recruited to Notch-responsive promoters upon Notch activation under hypoxic conditions. Taken together, these data provide molecular insights into how reduced oxygen levels control the cellular differentiation status and demonstrate a role for Notch in this process.

引用

页码：617 / 628

页数：12

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