Abstract
BackgroundLuman is a member of CREB3 (cAMP responsive element-binding) subfamily of the basic leucine-zipper (bZIP) transcription factors. It may play an important regulatory role during the decidualization process since Luman was highly expressed in the decidual cells. However, the exact molecular mechanisms of how Luman regulating decidualization is unknown.ResultsUsing an in vitro model, we prove that Luman knockdown significantly affects the decidualization process of mice endometrial stromal cells (ESCs) as the expression of two decidual markers PRL8a2 and PRL3c1 were repressed. We employed massively parallel RNA sequencing (RNA-Seq) to understand the changes in the transcriptional landscape associated with knockdown of Luman in ESCs during in vitro decidualization. We found significant dysregulation of genes related to protein processing in the endoplasmic reticulum (ER). Several genes involved in decidualization including bone morphogenetic proteins (e.g. BMP1, BMP4, BMP8A, BMP2, and BMP8B), growth factor-related genes (e.g. VEGFB, FGF10, and FGFR2), and transcription factors (IF4E, IF4A2, WNT4, WNT9A, ETS1, NOTCH1, IRX1, IDB1, IDB2, and IDB3), show altered expression. We also found that the knockdown of Luman is associated with increased expression of cell cycle-related genes including cycA1, cycB1, cycB2, CDK1, CDK2, and PLPK1, which resulted in an increased proportion of ESCs in the G1 phase. Differentially expressed genes (DEGs) were highly enriched on ECM-receptor interaction signaling, endoplasmic reticulum protein processing, focal adhesion, and PI3K-Akt signaling pathways.ConclusionsLuman knockdown results in widespread gene dysregulation during decidualization of ESCs. Genes involved in protein processing in ER, bone morphogenetic protein, growth factor, and cell cycle progression were identified as particularly important for explaining the decidual deficiency observed in this in vitro model. Therefore, this study provides clues as to the underlying mechanisms that may expand our understanding of gene regulation during decidualization.
Highlights
IntroductionLuman is a member of CREB3 (cAMP responsive element-binding) subfamily of the basic leucinezipper (bZIP) transcription factors
Luman is a member of CREB3 subfamily of the basic leucinezipper transcription factors
Luman expression in Endometrial stromal cell (ESC) during in vitro decidualization Our previous study has shown that Luman protein was expressed in decidual cells of the mouse uterus on Day 6 of pregnancy
Summary
Luman is a member of CREB3 (cAMP responsive element-binding) subfamily of the basic leucinezipper (bZIP) transcription factors. It may play an important regulatory role during the decidualization process since Luman was highly expressed in the decidual cells. After the attachment of embryo(s) to the uterine epithelium, the embryo(s) will breach the luminal epithelial barrier and invade into the underlying uterine stroma, which triggers extensive remodeling of the endometrial stromal compartment [2] This process is known as decidualization, characterized by the differentiation of stromal fibroblasts into specialized decidual cells that coordinate trophoblast invasion and placenta formation [3]. Various studies have shown that C/EBPβ is a key mediator of stromal cell proliferation and decidualization by regulating the expression of multiple cell cycle regulatory proteins [9, 10]
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