早期停育胚胎的滋养层细胞相关基因与特征分析

doi:10.16288/j.yczz.20-144

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Hereditas(Beijing) ›› 2020, Vol. 42 ›› Issue (10): 1004-1016.doi: 10.16288/j.yczz.20-144

• Research Article • Previous Articles Next Articles

Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation

Yue Zhang¹, Ying Feng², Fang Ma^1,³()

^1. Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu 610041, China
^2. West China School of Basic Medical Sciences & Forensic Medicine, Chengdu 610041, China;
^3. Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu 610041, China

Received:2020-08-08 Revised:2020-10-02 Online:2020-10-20 Published:2020-10-15
Contact: Ma Fang E-mail:mafangmed@126.com
Supported by:
Supported by the National Nature Science Foundation of China No(31771662);the National Science and Technology Major Project No(2018YFC1002803-3)

Abstract

Abstract:

Trophoblast cells play essential roles in the maintenance of normal embryo implantation, growth and development. The study of abnormal gene changes in trophoblastic cells from arrested embryos is helpful to understand the developmental mechanism of embryo developmental cessation or adverse pregnancy outcomes. In this study, we sequenced and analyzed the transcriptomes of the villi from ten women who have undergone abortion with either normal pregnancy or embryo development cessation. We found that there were 436 differentially expressed genes, of which 406 mRNA were significantly up-regulated and 32 mRNA were significantly down-regulated. Gene enrichment analysis showed that these genes were significantly enriched in immune-related functions and intercellular adhesion, such as lymphocyte activation, myeloid cell activation, extracellular matrix and collagen junction. And their potential regulatory pathways were enriched in terms of complement and coagulation cascade, extracellular matrix degradation. In addition, in this study the co-expression analysis of WGCNA was used to obtain the lncRNA with co-expression relationship with the differential genes. According to the different functions of the modules, two network diagrams were drawn, and four key genes were obtained, namely VSIG4, C1QC, CD36 and SPP1. These differential genes obtained in this study can be used as key molecules with potential effects on embryo development cessation. The enriched entries can provide a theoretical basis and new direction for further understanding of the etiology and mechanism of embryo development cessation or adverse pregnancy outcomes.

Key words: trophoblast, RNA-seq, enrichment analysis, genetic traits

Yue Zhang, Ying Feng, Fang Ma. Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation[J]. Hereditas(Beijing), 2020, 42(10): 1004-1016.

Figures/Tables 8

Table 1

Table 2

Fig. 1

Fig. 2

Fig. 3

Table 3

KEGG enrichment analysis of differential mRNAs (the top 10 signaling pathways with the highest confidence)"

通路二级分类(B类)	通路	P值	q值	通路号	富集到的基因
免疫系统 (immune system)	补体及凝血级联反应(complement and coagulation cascades)	3.70E-07	9.07E-05	ko04610	C7、CLU、F13A1、VSIG4、C1QC、ITGB2、ITGAM、C3AR1、C1QB、C1QA、C5AR1、CFD、CR1
信号分子与相互作用 (signaling molecules and interaction)	细胞外基质 (cell adhesion molecules)	3.78E-07	1.16E-03	ko04514	ITGAL、SPP1、CD4、PTPRC、SIGLEC1、NRCAM、MAG、CD36、LRRC4、VTCN1、ITGB2、NFASC、ITGAM、HLA-DOA、HLA-DRA、HLA-C、HLA-G、HLA-A、HLA-B
运输和分解代谢 (transport and catabolism)	吞噬体 (phagosome)	2.54E-06	2.07E-04	ko04145	MSR1、CORO1A、COMP、NCF2、CD36、TLR2、FCGR2A、FCGR1A、PLA2R1、ITGB2、CTSS、CYBB、ITGAM、CD14、HLA-DOA、HLA-DRA、HLA-C、HLA-G、HLA-A、HLA-B、MRC1、RAB7B
感染性疾病 (infectious diseases)	金黄色葡萄球菌感染 (Staphylococcus aureus infection)	3.84E-06	2.35E-04	ko05150	ITGAL、FCGR2A、FCGR1A、C1QC、ITGB2、ITGAM、FPR2、FPR1、C3AR1、C1QB、C1QA、C5AR1、CFD、HLA-DOA、HLA-DRA
感染性疾病 (infectious diseases)	阿米巴病 (amoebiasis)	6.45E-06	3.16E-04	ko05146	GNA15、LAMB4、LAMA1、TLR2、PLCB2、ITGB2、CXCL1、PRKCB、ITGAM、CD14、PIK3CD、RAB7B
免疫系统 (immune system)	血小板激活 (platelet activation)	1.59E-05	6.48E-04	ko04611	LCP2、PTGS1、P2RX1、PLCB2、PIK3R5、FCGR2A、FCER1G、PTGIR、GUCY1A3、SYK、PIK3CD、RASGRP1、PLCG2
感染性疾病 (infectious diseases)	肺结核 (tuberculosis)	3.59E-05	1.16E-03	ko05152	CD74、CORO1A、LSP1、TLR2、FCGR2A、FCGR1A、PLA2R1、FCER1G、ITGB2、CTSS、SYK、ITGAM、CD14、TLR1、CR1、HLA-DOA、HLA-DRA、MRC1
免疫系统 (immune system)	FcγR 介导的吞噬作用 (Fc gamma R-mediated phagocytosis)	2.01E-04	2.07E-04	ko04666	WAS、PTPRC、HCK、DOCK2、BIN1、FCGR2A、FCGR1A、PLPP3、SYK、PRKCB、PIK3CD、PLCG2
生长发育 (development)	破骨细胞分化 (osteoclast differentiation)	0.000123966	3.37E-03	ko04380	TYROBP、LCP2、SPI1、TREM2、LILRB1、LILRB5、NCF2、FCGR2A、FCGR1A、SYK、PIK3CD、CSF1、PLCG2、LILRA6
感染性疾病 (infectious diseases)	疟疾 (malaria)	0.000277305	6.79E-03	ko05144	ITGAL、COMP、CCL2、CD36、TLR2、ITGB2、CR1

Table 3

Fig. 4

Fig. 5

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序号	临床诊断	年龄(岁)	孕产次	孕周(d)	是否可探胎心	β-HCG(mIU/mL)
1	人工流产	24	G2P0⁺¹	42	胎芽不清	-
2	人工流产	34	G4P0⁺³	43	胎芽不清	-
3	人工流产	29	G3P1⁺¹	49	可见胎心搏动	-
4	人工流产	31	G2P1	47	可见胎心搏动	-
5	人工流产	28	-	51	可见胎心搏动	-
6	胚胎停育	30		55	未见胎心	11,951.4
7	胚胎停育	36	G2P1	50	未见胎心	12,612.1
8	胚胎停育	27	G1P0	57	未见胎心	69,220
9	胚胎停育	27	G1P0	80	未见胎心	-
10	胚胎停育	33	G1P0	59	未见胎心	32,594.4

序列	类型	基因名称	上游序列(5?→3?)	下游序列(5?→3?)
1	mRNA	C1QC	ATCCTGGGAAAAATGGCCCC	GAGGACCGCGTTGAATCTGA
2		VSIG4	TCCAGCAGGCAAAGTACCAG	GTTTCTGGACACGGAGCTCA
3		SPP1	GATGACCATGTGGACAGCCA	AACCACACTATCACCTCGGC
4		CD36	GACCGAGGAAGCCACTTTGA	TAAGCAGGTCTCCAACTGGC
5		NCKAP1L	TGTCTTCCACTCCCGAATGC	TGCAGTGGACAAAGTGAGCA
6		FGD2	TGCTACGCATTCCTCACTGG	ATAGAGCACGAGGGGGTCAT
7		LILRB5	ACCCTGCTGTGTCAGTCATG	GTAGGACCTGATTGCGCTGT
8		FOLR2	GCACCACAAGACAAAGCCAG	CAGGTTGGGTGAGCACTCAT
9		DPPA3	CCAGGGTCTCCACAAATGCT	ATTTCCCTGAGGACTGCTGC
10		MX1	TCGGAGGCTACAGGAAGACT	TTTGCGATGTCCACTTCGGA
11	lncRNA	CLRN1-AS1	GAAAGTCTGAAGCCAGGCCT	CTTTGGGCTTGCACAGTCAC
12		AC104809.4	CGTGGGCTCGTCTAAGTGTT	GCACTGAGCTGTTTGCAGTC
13		LINC01136	ACCTCAGAGGCTACCCACAT	AGAAGAAATCCAGGGGCTGC
14		USP27X-AS1	TGCAACCAGAGGAACTGCAA	AGGTGGACCTATGGGCTTCT

Related genes and characteristic analysis of trophoblast cells during early embryo developmental cessation

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