Transcriptomic Profiling of Trophoblast Fusion Using BeWo and JEG-3 Cell Lines

ABSTRACT: Introduction: In human placenta, alteration in trophoblast differentiation has a major impact on placental maintenance and integrity. Moreover, abnormal syncytial fusion seems to be implicated in the development of many complications including pre-eclampsia and intra-uterine growth restriction (IUGR). However, little is known about the mechanisms that control cytotrophoblast fusion into syncytiotrophoblast. BeWo cell line is commonly used to study placental function since it can be induced to form syncytium and secretes hormones. This fusion is triggered by cAMP or forskolin treatments. In contrast, JEG-3 cell line fails to undergo substantial fusion. Therefore, we will use BeWo and JEG-3 cells to identify a set of genes responsible of trophoblast fusion. Methods: BeWo and JEG-3 cells were treated with forskolin for 48 to induce fusion. RNA was extracted, hybridized to Affymetrix HuGene ST1.0 arrays and analyzed using system biology. Trophoblast differentiation was evaluated by real time PCR and immunocytochemistry analysis. Moreover, some of the identified genes were validated by real time PCR. Results: Our results identified a list of 32 altered genes in fused BeWo cells compared to JEG-3 cells after forskolin treatment. Among these genes, 4 were validated by real-time PCR including salt inducible Kinase 1 (SIK1) gene which is specifically upregulated in BeWo cells upon fusion. Moreover, using system biology analysis, SIK1 showed to be at the center of many biological and functional processes which suggest that it might play a major role in trophoblast differentiation. Conclusion: This study identified new target genes implicated in trophoblast fusion; a process implicated in the etiology of many pregnancy-related diseases such as preeclampsia, IUGR, and gestational diabetes.

ORGANISM(S): Homo sapiens

PROVIDER: GSE127170 | GEO | 2019/02/26

REPOSITORIES: GEO