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On-line Access: 2022-06-16

Received: 2021-12-07

Revision Accepted: 2022-05-04

Crosschecked: 2022-09-16

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Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Bin YU

https://orcid.org/0000-0001-7796-7314

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Journal of Zhejiang University SCIENCE B

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Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level


Author(s):  Bin ZHANG, Feng ZHANG, Fengying LU, Jing WANG, Wenbai ZHOU, Huihui WANG, Bin YU

Affiliation(s):  Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou 213000, China

Corresponding email(s):  binyu@njmu.edu.cn

Key Words:  Advanced maternal age (AMA); Pregnancy complications; Placenta; Trophoblast; Cell invasion; Serine protease inhibitor clade E member 1 (SERPINE1)


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Bin ZHANG, Feng ZHANG, Fengying LU, Jing WANG, Wenbai ZHOU, Huihui WANG, Bin YU. Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level[J]. Journal of Zhejiang University Science B, 2022, 23(3): 747-759.

@article{title="Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level",
author="Bin ZHANG, Feng ZHANG, Fengying LU, Jing WANG, Wenbai ZHOU, Huihui WANG, Bin YU",
journal="Journal of Zhejiang University Science B",
volume="23",
number="9",
pages="747-759",
year="2022",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2101024"
}

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%T Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level
%A Bin ZHANG
%A Feng ZHANG
%A Fengying LU
%A Jing WANG
%A Wenbai ZHOU
%A Huihui WANG
%A Bin YU
%J Journal of Zhejiang University SCIENCE B
%V 23
%N 9
%P 747-759
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%D 2022
%I Zhejiang University Press & Springer

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T1 - Reduced cell invasion may be a characteristic of placental defects in pregnant women of advanced maternal age at single-cell level
A1 - Bin ZHANG
A1 - Feng ZHANG
A1 - Fengying LU
A1 - Jing WANG
A1 - Wenbai ZHOU
A1 - Huihui WANG
A1 - Bin YU
J0 - Journal of Zhejiang University Science B
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Abstract: 
The mechanisms underlying pregnancy complications caused by advanced maternal age (AMA) remain unclear. We analyzed the cellular signature and transcriptomes of human placentas in AMA women to elucidate these mechanisms. Placental tissues from two AMA women and two controls were used for single-cell RNA-sequencing (scRNA-seq). Controls consisted of AMA women who did not experience any pregnancy complications and pregnant women below the age of 35 years without pregnancy complications. Trophoblast cells were obtained from the placentas of another six pregnant women (three AMA women and three controls), and in-vitro transwell assays were conducted to observe the cell invasion ability. Thirty additional samples (from 15 AMA women and 15 controls) were analyzed to verify the specific expression of serine protease inhibitor clade E member 1 (SERPINE1). Preliminary study of the role of SERPINE1 in cell invasion was carried out with HTR8-S/Vneo cells. High-quality transcriptomes of 27‍607 cells were detected. Three types of trophoblast cells were detected, which were further classified into eight subtypes according to differences in gene expression and Gene Ontology (GO) function. We identified 110 differentially expressed genes (DEGs) in trophoblast cells between the AMA and control groups, and the DEGs were enriched in multiple pathways related to cell invasion. In-vitro transwell assays suggested that the invading trophoblast cells in AMA women were reduced. SERPINE1 was specifically expressed in the trophoblast, and its expression was higher in AMA women (P<0.05). Transfection of human SERPINE1 (hSERPINE1) into HTR8-S/Vneo trophoblast cells showed fewer invading cells in the hSERPINE1 group. Impaired cell invasion may underlie the increased risk of adverse pregnancy outcomes in AMA women. Abnormal expression of SERPINE1 in extravillous trophoblast (EVT) cells appears to play an important role.

从单细胞水平揭示细胞侵袭减少可能是高龄孕妇胎盘缺陷特征

张玢,张峰,卢凤英,王晶,周文柏,王辉辉,虞斌
南京医科大学,常州医学中心,常州市妇幼保健院医学遗传科,中国常州市,213000
目的:目前高龄孕妇(advanced maternal age,AMA)妊娠风险增高的原因尚不清楚,本研究从单细胞水平解析AMA孕妇胎盘的细胞组成与转录组特征。
创新点:首次利用单细胞测序技术描述AMA孕妇胎盘的细胞图谱,探讨AMA孕妇滋养细胞及其细胞亚型的特征性变化。
方法:收集2名AMA和2名正常孕妇胎盘组织进行单细胞RNA测序(scRNA-seq)生物信息学分析。在此基础上,从6名孕妇(3名AMA孕妇和3名正常对照)胎盘分离培养滋养细胞,采用transwell实验观察细胞侵袭能力,同时观察SERPINE1的特异性表达。采用HTR8-S/Vneo细胞对SERPINE1在细胞侵袭中的作用进行初步研究。
结论:细胞浸润受损可能是AMA女性不良妊娠结局风险增加的原因。SERPINE1在EVT细胞中的异常表达似乎起着重要作用。

关键词组:高龄;妊娠并发症;胎盘;滋养细胞;细胞侵袭;SERPINE1

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

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