Mouse embryonic stem cells with aberrant transforming growth factor beta signalling exhibit impaired differentiation in vitro and in vivo.
Mouse embryonic stem cells with aberrant transforming growth factor beta signalling exhibit impaired differentiation in vitro and in vivo.
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具有异常转化生长因子β信号传导的小鼠胚胎干细胞在体外和体内表现出分化受损。
DOI：
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
C. Mummery
中科院分区：
文献类型：
--
作者：
M. Goumans;D. W. Oostwaard;F. Wianny;P. Savatier;A. Zwijsen;C. Mummery
胚胎干（ES）细胞对转化生长因子β（TGF β）具有抗性。我们以前已经表明，它们缺乏II型结合受体（T β RII），在这方面类似于小鼠胚胎4.5-7.5天后（dpc）的内细胞团和外胚层细胞;然而，它们确实表达I型（alk-5）信号受体。在这里，我们表明，在几种肿瘤细胞系，稳定转染的wtT β RII是不足以使ES细胞成为生物敏感的TGF β。我们分析了已知参与TGF β信号传导（Smads）和TGF β介导的细胞周期调控的几种下游分子的表达。（细胞周期蛋白D），并显示这些分子的上调与（i）纤溶酶原激活物抑制剂-1（派-1）合成的增加和（ii）生长抑制相关，加入TGF β 1后。这些TGF β反应在表达显性阴性（截短）T β RII（Δ T β RII）的ES细胞系中降低。对照和wtT β RII表达ES细胞的分化模式在单层培养和胚状体中无法区分，但在δ T β RII ES细胞中，响应于加入视黄酸（RA）和去除白血病抑制因子（LIF）而在单层培养中形成中胚层衍生物的能力丧失，仅形成内胚层样细胞。然而，T β RII和Δ T β RII ES细胞在与桑椹胚阶段宿主聚集后在嵌合体胚胎中分化时，与对照ES细胞都是可区分的。含有突变细胞的孕体，从假孕雌性中回收，相当于9.5 dpc，表现出高度缺陷的卵黄囊发育;最引人注目的是，没有血管存在，此外，含有wtT β RII的ES细胞衍生物的卵黄囊被破坏，缺乏造血细胞。了解TGF β信号在小鼠早期发育的影响进行了讨论。
Embryonic stem (ES) cells are resistant to transforming growth factor beta (TGF beta). We have shown previously that they lack type-II binding receptors (T beta RII) and in this respect resemble the inner cell mass and ectoderm cells of mouse embryos 4.5-7.5 days post coitum (dpc); they do however express type-I (alk-5) signalling receptors. Here we show that in contrast to several tumour cell lines, stable transfection of wtT beta RII is not sufficient for ES cells to become biologically sensitive to TGF beta. We analysed the expression of several down-stream molecules known to be involved in TGF beta signalling (Smads) and TGF beta-mediated cell cycle regulation (cyclins D) during the differentiation of control and wtT beta RII-expressing ES cells and showed that upregulation of these molecules correlated with (i) an increase in plasminogen activator inhibitor-1 (PAI-1) synthesis and (ii) growth inhibition, following addition of TGF beta 1. These TGF beta responses were reduced in an ES cell line expressing a dominant negative (truncated) T beta RII (delta T beta RII). The differentiation pattern of control and wtT beta RII-expressing ES cells was indistinguishable in monolayer culture and as embryoid bodies, but in delta T beta RII ES cells, the capacity to form mesodermal derivatives in monolayer cultures in response to the addition of retinoic acid (RA) and removal of leukemia inhibitory factor (LIF) was lost, and only endoderm-like cells formed. The T beta RII and delta T beta RII ES cells were, however, both distinguishable from control ES cells when allowed to differentiate in chimaeric embryos following aggregation with morula-stage hosts. Conceptuses containing mutant cells, recovered from pseudopregnant females at the equivalent of 9.5 dpc, exhibited highly defective yolk sac development; most strikingly, no blood vessels were present and in addition the yolk sacs with derivatives of ES cells containing wtT beta RII were blistered and lacked haematopoietic cells. The implications for understanding TGF beta signalling in early mouse development are discussed.
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DOI：
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发表时间：
1986-03
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
R. Ignotz;J. Massagué
通讯作者：
R. Ignotz;J. Massagué
植入后小鼠胚胎中血栓调节蛋白的发育调控基因表达。
DOI：
10.1242/dev.122.7.2271
发表时间：
1996
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Weiler-Guettler,H;Aird,WC;Rayburn,H;Husain,M;Rosenberg,RD
通讯作者：
Rosenberg,RD
影响因子：
10.5
作者：
FRIEDRICH, G;SORIANO, P
通讯作者：
SORIANO, P
转化生长因子β II 型受体的表达可降低人乳腺癌MCF-7 细胞的恶性程度。
DOI：
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发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sun,L;Wu,G;Willson,JK;Zborowska,E;Yang,J;Rajkarunanayake,I;Wang,J;Gentry,LE;Wang,XF;Brattain,MG
通讯作者：
Brattain,MG
小鼠发育过程中 TGF β 3 RNA 表达的原位杂交分析：与 TGF β 1 和 β 2 的比较研究。
DOI：
10.1242/dev.110.2.609
发表时间：
1990
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Pelton,RW;Dickinson,ME;Moses,HL;Hogan,BL
通讯作者：
Hogan,BL