Maurya Vineet K, Popli Pooja, Nikolai Bryan C, Lonard David M, Kommagani Ramakrishna, O'Malley Bert W, Lydon John P
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Cells. 2025 Jul 4;14(13):1024. doi: 10.3390/cells14131024.
Defective placentation is a recognized etiology for several gestational complications that include early pregnancy loss, preeclampsia, and intrauterine growth restriction. Sustained viability, migration, and invasion are essential cellular properties for embryonic extravillous trophoblasts to execute their roles in placental development and function, while derailment of these cellular processes is linked to placental disorders. Although the cellular functions of extravillous trophoblasts are well recognized, our understanding of the pivotal molecular determinants of these functions is incomplete. Using the HTR-8/SVneo immortalized human extravillous trophoblast cell line, we report that steroid receptor coactivator-2 (SRC-2), a coregulator of transcription factor-mediated gene expression, is essential for extravillous trophoblast cell viability, motility, and invasion. Genome-scale transcriptomics identified an SRC-2-dependent transcriptome in HTR-8/SVneo cells that encodes a diverse spectrum of proteins involved in placental tissue development and function. Underscoring the utility of this transcriptomic dataset, we demonstrate that WNT family member 9A (WNT 9A) is not only regulated by SRC-2 but is also crucial for maintaining many of the above SRC-2-dependent cellular functions of human extravillous trophoblasts.
胎盘形成缺陷是多种妊娠并发症的公认病因，这些并发症包括早期妊娠丢失、子痫前期和宫内生长受限。持续的生存能力、迁移和侵袭是胚胎绒毛外滋养层细胞在胎盘发育和功能中发挥作用所必需的细胞特性，而这些细胞过程的紊乱与胎盘疾病有关。尽管绒毛外滋养层细胞的细胞功能已得到充分认识，但我们对这些功能的关键分子决定因素的理解并不完整。利用HTR-8/SVneo永生化人绒毛外滋养层细胞系，我们报告类固醇受体辅激活因子-2（SRC-2），一种转录因子介导的基因表达的共调节因子，对绒毛外滋养层细胞的生存能力、运动性和侵袭至关重要。基因组规模的转录组学在HTR-8/SVneo细胞中鉴定出一个SRC-2依赖性转录组，该转录组编码参与胎盘组织发育和功能的多种蛋白质。强调这个转录组数据集的实用性，我们证明WNT家族成员9A（WNT 9A）不仅受SRC-2调节，而且对维持人类绒毛外滋养层细胞上述许多SRC-2依赖性细胞功能也至关重要。
