Preeclampsia-Associated Alteration of DNA Methylation in Fetal Endothelial Progenitor Cells

被引：0

作者：

Brodowski, Lars ^{[1
]}

Zindler, Tristan ^{[2
]}

von Hardenberg, Sandra ^{[1
]}

Schroeder-Heurich, Bianca ^{[1
]}

von Kaisenberg, Constantin S. ^{[1
]}

Frieling, Helge ^{[2
]}

Hubei, Carl A. ^{[3
]}

Doerk, Thilo ^{[1
]}

von Versen-Hoeynck, Frauke ^{[1
]}

机构：

[1] Hannover Med Sch, Dept Obstet & Gynecol, Hannover, Germany

[2] Hannover Med Sch, Psychiat Social Psychiat & Psychotherapy, Hannover, Germany

[3] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Magee Womens Res Inst, Sch Med, Pittsburgh, PA USA

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2019年 / 7卷

基金：

美国国家卫生研究院;

关键词：

preeclampsia; DNA methylation; epigenetics; endothelial colony-forming cells; fetal programming; LONG NONCODING RNA; MEF2 TRANSCRIPTION FACTORS; EXPRESSION PATTERNS; HUMAN PLACENTAS; GROWTH; HYPOMETHYLATION; APOPTOSIS; INVASION; REGIONS; SYSTEM;

D O I：

10.3389/fceil.2019.00032

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Objective: The pregnancy complication preeclampsia represents an independent risk factor for cardiovascular disease. Our previous research shows a diminished function of fetal endothelial colony-forming cells (ECFC), a proliferative subgroup of endothelial progenitor cells (EPC) in preeclampsia. The aim of this study was to further investigate whether DNA methylation of fetal EPC is affected in preeclampsia. Methods: The genomic methylation pattern of fetal ECFC from uncomplicated and preeclamptic pregnancies was compared for 865918 CpG sites, and genes were classified into gene networks. Low and advanced cell culture passages were compared to explore whether expansion of fetal ECFC in cell culture leads to changes in global methylation status and if methylation characteristics in preeclampsia are maintained with increasing passage. Results: A differential methylation pattern of fetal ECFC from preeclampsia compared to uncomplicated pregnancy was detected for a total of 1266 CpG sites in passage 3, and for 2362 sites in passage 5. Key features of primary networks implicated by methylation differences included cell metabolism, cell cycle and transcription and, more specifically, genes involved in cell-cell interaction and Wnt signaling. We identified an overlap between differentially regulated pathways in preeclampsia and cardiovascular system development and function. Cell culture passages 3 and 5 showed similar gene network profiles, and 1260 out of 1266 preeclampsia-associated methylation changes detected in passage 3 were confirmed in passage 5. Conclusion: Methylation modification caused by preeclampsia is stable and detectable even in higher cell culture passages. An epigenetically modified endothelial precursor may influence both normal morphogenesis and postnatal vascular repair capacity. Further studies on epigenetic modifications in complicated pregnancies are needed to facilitate development of EPC based therapies for cardiovascular alterations.

引用

页数：14

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