Connexin31-deficient trophoblast stem cells: a model to analyze the role of gap junction communication in mouse placental development
Connexin31-deficient trophoblast stem cells: a model to analyze the role of gap junction communication in mouse placental development
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DOI：
10.1016/j.ydbio.2004.04.037
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发表时间：
2004-09-01
影响因子：
2.7
通讯作者：
Winterhager, E
中科院分区：
文献类型：
--
作者：
Kibschull, M;Nassiry, M;Winterhager, E
在啮齿类动物胎盘发育过程中，连接蛋白（Cx）的表达受到严格的时空调控。着床后，Cx 31表征早期滋养层细胞谱系，并在胎盘发育直至出生期间由海绵滋养层表达。Cx 31基因的失活导致短暂的胎盘畸形，滋养层细胞谱系分化不平衡，有利于巨细胞[Dev. 231（2001）334]。在这项研究中，我们表明，滋养层干细胞（TS）细胞表现出相同的连接蛋白的表达发现在滋养层细胞谱系分化。未分化的TS细胞仅表达Cx 31蛋白和Cx 31。我是成绩单。TS细胞分化后，胎盘特异性Cx 26和Cx43被诱导。Cx 31敲除TS细胞显示与对照相比加速的向巨细胞的分化过程，这由连接蛋白和标记基因如Mash 2、Pl-1和Tpbpa的表达的总体变化指示。此外，Cx 31敲除TS细胞在分化后增殖显著降低。野生型和Cx 31基因敲除的TS细胞在注射到裸鼠体内时都能够侵入和侵蚀宿主血管。我们的结论是，在滋养层细胞谱系分化，Cx 31缝隙连接通道参与维持增殖的二倍体滋养层细胞群。(C)2004年爱思唯尔公司All rights reserved.
The connexin (Cx) expression during placental development in rodents is subject to exacting spatiotemporal regulation. Following implantation, Cx31 characterizes the early trophoblast cell lineage and is expressed by the spongiotrophoblast during placental development until birth. Inactivation of the Cx31 gene results in a transient placental dysmorphogenesis with an imbalance in the trophoblast cell lineage differentiation in favor to giant cells [Dev. Biol. 231 (2001) 334]. In this study, we show that trophoblast stem (TS) cells exhibit the same connexin expression found in trophoblast cell lineage differentiation. Undifferentiated TS cells exclusively express Cx31 protein and Cx31. I transcripts. Upon differentiation of TS cells, placental-specific Cx26 and Cx43 are induced. Cx31 knockout TS cells revealed an accelerated differentiation process to giant cells compared to controls, indicated by an overall shift in expression of connexins and marker genes such as Mash2, Pl-1, and Tpbpa. Moreover, proliferation was significantly reduced in Cx31 knockout TS cells upon differentiation. Both wild type and Cx31 knockout TS cells are able to invade and erode host vessels when injected into nude mice. We conclude that during trophoblast cell lineage differentiation, the Cx31 gap junction channel is involved in maintaining the proliferative diploid trophoblast cell population. (C) 2004 Elsevier Inc. All rights reserved.