Center for genetics and Developmental Systems Biology, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence and Guangdong Key Laboratory of Psychiatric Disorders, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Theranostics. 2021 Mar 5;11(10):5028-5044. doi: 10.7150/thno.56141. eCollection 2021.
Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Although several transcriptome studies have been done on placentae from PE patients, only a small number of differentially expressed genes have been identified due to very small sample sizes and no distinguishing of clinical subtypes. We carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for dysregulated genes and the molecular network and pathways they are involved in. We identified two functionally distinct sets of dysregulated genes in the two major subtypes: 2,977 differentially expressed genes in early-onset severe preeclampsia, which are enriched with metabolism-related pathways, notably transporter functions; and 375 differentially expressed genes in late-onset severe preeclampsia, which are enriched with immune-related pathways. We also identified some key transcription factors, which may drive the widespread gene dysregulation in both early-onset and late-onset patients. These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors. A few regulators may be the key drivers of the dysregulated molecular pathways.
患有子痫前期的患者表现出一系列的发病时间和临床严重程度，但早发型和晚发型临床亚型的潜在分子基础尚不清楚。尽管已经对患有子痫前期的患者的胎盘进行了几项转录组研究，但由于样本量非常小，且没有区分临床亚型，因此仅鉴定出少数差异表达基因。我们对 65 个高质量的胎盘样本进行了 RNA-seq 分析，其中包括 33 个来自 30 名患者和 32 个来自 30 名对照者的样本，以寻找失调基因及其参与的分子网络和途径。我们在两个主要亚型中鉴定出了两组功能不同的失调基因：在早发型重度子痫前期中，有 2977 个差异表达基因，这些基因与代谢相关途径（特别是转运蛋白功能）富集；在晚发型重度子痫前期中，有 375 个差异表达基因，这些基因与免疫相关途径富集。我们还鉴定出了一些关键的转录因子，这些转录因子可能驱动早发型和晚发型患者的广泛基因失调。这些结果表明，早发型和晚发型重度子痫前期具有不同的分子机制，而晚发型轻度子痫前期可能没有胎盘特异性的因果因素。少数调节剂可能是失调分子途径的关键驱动因素。
