Elevated expression of glycolytic genes as a prominent feature of early-onset preeclampsia: insights from integrative transcriptomic analysis

作者全名："He, Jie; Yang, Huan; Liu, Zheng; Chen, Miaomiao; Ye, Ying; Tao, Yuelan; Li, Shuhong; Fang, Jie; Xu, Jiacheng; Wu, Xiafei; Qi, Hongbo"

作者地址："[He, Jie; Liu, Zheng; Tao, Yuelan; Fang, Jie; Xu, Jiacheng; Wu, Xiafei; Qi, Hongbo] Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, Chongqing, Peoples R China; [He, Jie; Liu, Zheng; Tao, Yuelan; Fang, Jie; Xu, Jiacheng; Wu, Xiafei; Qi, Hongbo] Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Chongqing, Peoples R China; [He, Jie; Liu, Zheng; Tao, Yuelan; Fang, Jie; Xu, Jiacheng; Wu, Xiafei; Qi, Hongbo] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chinese Minist Educ, Chongqing, Peoples R China; [Yang, Huan] Chongqing Univ, Three Gorges Hosp, Dept Obstet, Chongqing, Peoples R China; [Chen, Miaomiao] Maternal & Child Hlth Hosp Hubei Prov, Wuhan, Peoples R China; [Ye, Ying] Chongqing Med Univ, Affiliated Hosp 2, Dept Cardiothorac Surg, Chongqing, Peoples R China; [Li, Shuhong] Chengdu Second Peoples Hosp, Dept Oncol, Chengdu, Peoples R China; [Qi, Hongbo] Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, Chongqing, Peoples R China"

通信作者："Qi, HB (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Obstet, Chongqing, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Maternal & Fetal Med, Chongqing, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chinese Minist Educ, Chongqing, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Dept Obstet & Gynecol, Chongqing, Peoples R China."

来源：FRONTIERS IN MOLECULAR BIOSCIENCES

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001077567000001

JCR分区：Q2

影响因子：3.9

年份：2023

卷号：10

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：preeclampsia; placenta; gestational hypertension; transcriptomics; microarray; single-cell sequencing

摘要："Introduction: Preeclampsia (PE), a notable pregnancy-related disorder, leads to 40,000+ maternal deaths yearly. Recent research shows PE divides into early-onset (EOPE) and late-onset (LOPE) subtypes, each with distinct clinical features and outcomes. However, the molecular characteristics of various subtypes are currently subject to debate and are not consistent.Methods: We integrated transcriptomic expression data from a total of 372 placental samples across 8 publicly available databases via combat algorithm. Then, a variety of strategies including Random Forest Recursive Feature Elimination (RF-RFE), differential analysis, oposSOM, and Weighted Correlation Network Analysis were employed to identify the characteristic genes of the EOPE and LOPE subtypes. Finally, we conducted in vitro experiments on the key gene HK2 in HTR8/SVneo cells to explore its function.Results: Our results revealed a complex classification of PE placental samples, wherein EOPE manifests as a highly homogeneous sample group characterized by hypoxia and HIF1A activation. Among the core features is the upregulation of glycolysis-related genes, particularly HK2, in the placenta-an observation corroborated by independent validation data and single-cell data. Building on the pronounced correlation between HK2 and EOPE, we conducted in vitro experiments to assess the potential functional impact of HK2 on trophoblast cells. Additionally, the LOPE samples exhibit strong heterogeneity and lack distinct features, suggesting a complex molecular makeup for this subtype. Unsupervised clustering analysis indicates that LOPE likely comprises at least two distinct subtypes, linked to cell-environment interaction and cytokine and protein modification functionalities.Discussion: In summary, these findings elucidate potential mechanistic differences between the two PE subtypes, lend support to the hypothesis of classifying PE based on gestational weeks, and emphasize the potential significant role of glycolysis-related genes, especially HK2 in EOPE."

基金机构：This work was made possible by the funding provided by the Joint Funds of the National Natural Science Foundation of China (No. U21A20346) and the General Program of the National Natural Science Foundation of China (No. 82171662). [U21A20346]; National Natural Science Foundation of China [82171662]; General Program of the National Natural Science Foundation of China

基金资助正文：We extend our sincere gratitude to all the individuals who contributed to this study. We would like to express our appreciation for the support received from the "111 program" of the Ministry of Education P.R.C and the State Administration of Foreign Experts Affairs P.R.C. We also extend our heartfelt thanks to the participants who graciously devoted their time and energy to make this study possible.r This work was made possible by the funding provided by the Joint Funds of the National Natural Science Foundation of China (No. U21A20346) and the General Program of the National Natural Science Foundation of China (No. 82171662).