Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast
Glial cell missing-1 transcription factor is required for the differentiation of the human trophoblast
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DOI：
10.1038/cdd.2009.1
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发表时间：
2009-05-01
影响因子：
12.4
通讯作者：
Kingdom, J.
中科院分区：
文献类型：
--
作者：
Baczyk, D.;Drewlo, S.;Kingdom, J.
哺乳动物胎盘形成是一个高度调控的过程，依赖于特定滋养层细胞谱系的正常发育。两种主要类型的滋养层，绒毛和绒毛外，在分化过程中显示有丝分裂停滞。在小鼠中，转录因子，胶质细胞缺失-1（Gcm 1），阻止有丝分裂，是合胞体滋养层形成和迷路形态发生所必需的，迷路相当于绒毛胎盘。人类同源物GCM 1具有类似的表达模式，但其功能目前尚不清楚。我们研究了GCM 1在人源BeWo绒毛膜癌细胞系和妊娠早期人胎盘绒毛和绒毛外外植体中的功能。GCM 1表达被siRNA和反义寡核苷酸方法抑制或被毛喉素处理上调。GCM 1的抑制导致增殖率增加，但阻止了合胞体裸露的漂浮绒毛外植体中的新生合胞体滋养层形成。GCM 1抑制防止绒毛外分化沿着侵袭途径在绒毛外外植体基质胶。相比之下，毛喉素诱导的GCM 1的表达降低了增殖率，增加了漂浮绒毛外植体模型中的合胞率。我们的研究表明，GCM 1在人类滋养层细胞的维持，发育和更新中具有独特的作用。GCM 1表达或调节的改变可以解释两种不同的严重胎盘功能不全综合征的几个方面，即先兆子痫和宫内生长受限，这导致极端早产。
Mammalian placentation is a highly regulated process and is dependent on the proper development of specific trophoblast cell lineages. The two major types of trophoblast, villous and extravillous, show mitotic arrest during differentiation. In mice, the transcription factor, glial cell missing-1 (Gcm1), blocks mitosis and is required for syncytiotrophoblast formation and morphogenesis of the labyrinth, the murine equivalent of the villous placenta. The human homolog GCM1 has an analogous expression pattern, but its function is presently unknown. We studied GCM1 function in the human-derived BeWo choriocarcinoma cell line and in first trimester human placental villous and extravillous explants. The GCM1 expression was either inhibited by siRNA and antisense oligonucleotides methods or upregulated by forskolin treatment. Inhibition of GCM1 resulted in an increased rate of proliferation, but prevented de novo syncytiotrophoblast formation in syncytially denuded floating villous explants. GCM1 inhibition prevented extravillous differentiation along the invasive pathway in extravillous explants on matrigel. By contrast, forskolin-induced expression of GCM1 reduced the rate of proliferation and increased the rate of syncytialization in the floating villous explant model. Our studies show that GCM1 has a distinct role in the maintenance, development and turnover of the human trophoblast. Alterations in GCM1 expression or regulation may explain several aspects of two divergent severe placental insufficiency syndromes, namely preeclampsia and intrauterine growth restriction, which cause extreme preterm birth.