Integration of Gene Expression Microarrays and Single-Cell Transcriptomics to Identify Intercellular Communication in the Endometrium of Recurrent Implantation Failure Patients

doi:10.12280/gjszjk.20240037

Abstract

Abstract:

Objective: To explore the key genes related to patients with recurrent implantation failure (RIF) using bioinformatics analysis, to identify cell subpopulations and cell-cell communications in human endometrium, and to discuss the impact on endometrial receptivity. Methods: The GSE103465 dataset, GSE183837 dataset and GSE223672 dataset were downloaded from the Gene Expression Omnibus (GEO) database as research samples. Endometrial tissue data from RIF patients and control females were utilized. R language and Perl scripts were employed to conduct the quality analysis on the raw data, and the limma package was utilized for differential gene selection. The selected differentially expressed genes were subjected to gene ontology (GO) and Kyoto encyclopedia of genes and genome (KEGG) analysis, Protein-Protein Interaction Networks (PPI) construction and core gene selection. Using R language-related packages, single-cell annotation and classification were performed, followed by the construction of an intercellular communication map. Results: The identified key genes included RPF2, DDX27, PWP2, CDC5L, NOP2, DCAF13, CEBPZ, FTSJ1, GNL3L, and NSUN2. The main cell types in the endometrium of patients with RIF were identified as epithelial cells, NK cells, granulocyte-monocyte progenitors, endothelial cells, and smooth muscle cells. The enriched pathways involving GRN, SPP1, PTN, MIF, MK signaling pathways participate in the intercellular communication through receptor-ligand pairs. Conclusions: The impaired endometrial receptivity in RIF patients is associated with aberrant RNA modification and processing and epigenetic modification errors, as well as inflammatory response and decreased metabolism. Intercellular communication reveals that endometrial epithelial cells in RIF patients have a decreased capacity for osteoblastin-integrin-mediated adhesion and invasion, which may be the cause of embryo implantation failure.

Key words: Embryo implantation, Embryo transfer, Computational biology, Genes, Cell communication, Endometrial receptivity

WU Chun-lei, ZHAO Xiao-li, QIU Yun-huan, WANG Bao-juan, DONG Rong, LI Kai-xi, XIA Tian. Integration of Gene Expression Microarrays and Single-Cell Transcriptomics to Identify Intercellular Communication in the Endometrium of Recurrent Implantation Failure Patients[J]. Journal of International Reproductive Health/Family Planning, 2024, 43(4): 265-273.

Figures/Tables 10

References 31

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数据集ID	平台	组织来源	RIF组/ 对照组（例）	取材时间	数据类型
GSE103465	GPL16043	子宫内膜	3/3	排卵后5 d	基因芯片
GSE183837	GPL24676	子宫内膜	6/3	排卵后5 d	单细胞转录组
GSE223672	GPL24676	子宫内膜	3/0	排卵后5 d	单细胞转录组

数据集ID	平台	组织来源	RIF组/ 对照组（例）	取材时间	数据类型
GSE103465	GPL16043	子宫内膜	3/3	排卵后5 d	基因芯片
GSE183837	GPL24676	子宫内膜	6/3	排卵后5 d	单细胞转录组
GSE223672	GPL24676	子宫内膜	3/0	排卵后5 d	单细胞转录组

上调基因		下调基因
Gene Symbol	logFC	Gene Symbol	logFC
SNORD89	4.20	PAEP	-4.95
HOXA6	2.71	C3	-3.55
KIAA1731	2.55	ESYT1	-2.49
LOC728741	2.54	NNMT	-2.49
SNORA54	2.36	DEPDC6	-2.49
POMZP3	2.35	NFKBIZ	-2.47
HOXD4	2.33	FHDC1	-2.40
BEND5	2.12	RP2	-2.20
POSTN	2.07	ATP13A3	-2.18
CIR1	1.80	PYGL	-2.17

上调基因		下调基因
Gene Symbol	logFC	Gene Symbol	logFC
SNORD89	4.20	PAEP	-4.95
HOXA6	2.71	C3	-3.55
KIAA1731	2.55	ESYT1	-2.49
LOC728741	2.54	NNMT	-2.49
SNORA54	2.36	DEPDC6	-2.49
POMZP3	2.35	NFKBIZ	-2.47
HOXD4	2.33	FHDC1	-2.40
BEND5	2.12	RP2	-2.20
POSTN	2.07	ATP13A3	-2.18
CIR1	1.80	PYGL	-2.17

上皮细胞		自然杀伤细胞		GMP		内皮细胞		平滑肌细胞
表达情况	基因	表达情况	基因	表达情况	基因	表达情况	基因	表达情况	基因
下调	MT-CO2	上调	NKG7	上调	CFD	上调	IGFBP7	下调	S100A10
下调	MALAT1	上调	CCL4	上调	IGFBP2	上调	A2M	下调	ATP5F1E