Epigenetic and gene expression analysis of cytotrophoblasts from term HDP placenta

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22943
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Tohoku University
• Principal Investigator: Kobayashi Eri 東北大学, 医学系研究科, 助教 (70634971)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 妊娠高血圧症候群 / エピゲノム

Outline of Final Research Achievements

We analyzed CT cells sorted from term placenta of HDP and uncomplicated pregnancies. RNA-seq and miRNA-seq showed differential expression in several regions, but mRNA and miRNA expressions were largely unchanged between CT cells from normal and HDP term placenta. Histone modifications detected by CUT&TAG-seq, including H3K4me3, H3K4m1, H3K27ac, H3K36me3, H3K27me and H3K9me3, were similar between HDP and normal term CT cells. Limited differential DNA methylation was found in the results of methyl-seq either. These results suggests that there is negligible difference in gene expression and epigenomic modification between HDP and normal CT cells obtained from term placenta. This implies that EVTs and STs differentiate from CT cells are responsible for HDP development.

Free Research Field

産婦人科学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究により、満期胎盤由来のCT細胞では正常群とHDP群の間で遺伝子発現やエピゲノム修飾に大きな差がない事が明らかになった。CT細胞は増殖を繰り返し分化する事でEVT細胞やST細胞を供給する事が主な役割である。EVT細胞は母体組織に浸潤し血管を拡張する役割を担うことから、その機能不全は血管のリモデリング不全によりHDP発症に繋がる可能性がある。ST細胞は母体との間のガス栄養交換及びホルモン産生を行い、HDP患者の血中で増加し血圧を上昇させるsFLT1もST細胞から分泌される。今回得られた結果はHDP発症につながるエピゲノム修飾の変化はEVT細胞やST細胞で起きている可能性を示唆している。