Overexpression of bone morphogenetic protein 4 in STO fibroblast feeder cells represses the proliferation of mouse embryonic stem cells in vitro.
Overexpression of bone morphogenetic protein 4 in STO fibroblast feeder cells represses the proliferation of mouse embryonic stem cells in vitro.
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DOI：
10.3858/emm.2012.44.7.052
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发表时间：
2012-07-31
影响因子：
12.8
通讯作者：
Han IS
中科院分区：
文献类型：
--
作者：
Kim GH;Lee GR;Choi HI;Park NH;Chung HT;Han IS
胚胎干细胞(ESCs)可以在小鼠STO成纤维细胞饲养层上体外繁殖。STO细胞分泌几种细胞因子，这些细胞因子是ESCs维持其未分化状态所必需的。在这项研究中，我们发现小鼠胚胎干细胞(MESCs)在含有显性-阴性突变形式的IκB(rAd-DNIκB)的腺病毒感染的STO细胞上培养具有显著的生长抑制作用。这种对κB信号通路的阻断导致小鼠胚胎干细胞的[~3H]胸腺嘧啶核苷掺入和集落形成显著降低。STO细胞分泌细胞因子的表达谱显示，携带显性负性IκB基因的腺病毒载体(Rad-DNIκB)感染STO细胞后，骨形态发生蛋白4(BMP4)的转录水平增加。这些结果表明，NF-κB信号通路抑制了滋养细胞中BMP4的表达。Rad-DNISTO B感染的κ细胞的条件培养液也显著减少了mESCs的集落大小。加入BMP4可抑制条件培养液中培养的小鼠胚胎干细胞的集落形成。我们的发现表明，条件培养液中过多的BMP4也抑制了mESCs的增殖。
Embryonic stem cells (ESCs) can be propagated in vitro on feeder layers of mouse STO fibroblast cells. The STO cells secrete several cytokines that are essential for ESCs to maintain their undifferentiated state. In this study, we found significant growth inhibition of mouse ESCs (mESCs) cultured on STO cells infected with adenovirus containing a dominant-negative mutant form of IκB (rAd-dnIκB). This blockage of the NF-κB signal pathway in STO cells led to a significant decrease in [3H]thymidine incorporation and colony formation of mESCs. Expression profile of cytokines secreted from the STO cells revealed an increase in the bone morphogenetic protein4 (BMP4) transcript level in the STO cells infected with adenoviral vector encoding dominant negative IκB (rAd-dnIκB). These results suggested that the NF-κB signaling pathway represses expression of BMP4 in STO feeder cells. Conditioned medium from the rAd-dnIκB-infected STO cells also significantly reduced the colony size of mESCs. Addition of BMP4 prevented colony formation of mESCs cultured in the conditioned medium. Our finding suggested that an excess of BMP4 in the conditioned medium also inhibits proliferation of mESCs.
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影响因子：
64.5
作者：
VAINIO, S;KARAVANOVA, I;THESLEFF, I
通讯作者：
THESLEFF, I
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
4.6
作者：
Pearson, Stella;Sroczynska, Patrycja;Kouskoff, Valerie
通讯作者：
Kouskoff, Valerie
影响因子：
2.7
作者：
Hao, J;Li, TG;Zhao, GQ
通讯作者：
Zhao, GQ
DOI：
10.1073/pnas.0401367101
发表时间：
2004-04-20
影响因子：
11.1
作者：
Qi, XX;Li, TG;Zhao, GQ
通讯作者：
Zhao, GQ