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Abstract：
Premature ovarian insufficiency (POI) is one of the most common causes of female infertility and the etiology is highly heterogeneous. Most cases are idiopathic and the pathogenesis remains unclear. Previous studies proved that the immune system plays a crucial role in POI. However, the precise role of immune system remains unclear. This study aimed to analyze the characteristics of peripheral blood mononuclear cells (PBMC) from patients with POI by single-cell RNA sequencing (scRNA-seq) and to explore the potential involvement of immune response in idiopathic POI.
PBMC was collected from three normal subjects and three patients with POI. PBMC was subjected to scRNA-seq to identify cell clusters and differently expressed genes (DEGs). Enrichment analysis and cell-cell communication analysis were performed to explore the most active biological function in the immune cells of patients with POI.
In total, 22 cell clusters and 10 cell types were identified in the two groups. Compared with normal subjects, the percentage of classical monocytes and NK cells was decreased, the abundance of plasma B cells was increased, and CD4/CD8 ratio was significantly higher in POI. Furthermore, upregulation of IGKC, IFITM1, CD69, JUND and downregulation of LYZ, GNLY, VCAN, and S100A9 were identified, which were enriched in NK cell-mediated cytotoxicity, antigen processing and presentation, and IL-17 signaling pathway. Among them, IGHM and LYZ were respectively the most significantly upregulated and downregulated genes among all cell clusters of POI. The strength of cell-cell communication differed between the healthy subjects and patients with POI, and multiple signaling pathways were assessed. The TNF pathway was found to be unique in POI with classical monocytes being the major target and source of TNF signaling.
Dysfunction of cellular immunity is related to idiopathic POI. Monocytes, NK cells, and B cells, and their enriched differential genes may play a role in the development of idiopathic POI. These findings provide novel mechanistic insight for understanding the pathogenesis of POI.
PBMC was collected from three normal subjects and three patients with POI. PBMC was subjected to scRNA-seq to identify cell clusters and differently expressed genes (DEGs). Enrichment analysis and cell-cell communication analysis were performed to explore the most active biological function in the immune cells of patients with POI.
In total, 22 cell clusters and 10 cell types were identified in the two groups. Compared with normal subjects, the percentage of classical monocytes and NK cells was decreased, the abundance of plasma B cells was increased, and CD4/CD8 ratio was significantly higher in POI. Furthermore, upregulation of IGKC, IFITM1, CD69, JUND and downregulation of LYZ, GNLY, VCAN, and S100A9 were identified, which were enriched in NK cell-mediated cytotoxicity, antigen processing and presentation, and IL-17 signaling pathway. Among them, IGHM and LYZ were respectively the most significantly upregulated and downregulated genes among all cell clusters of POI. The strength of cell-cell communication differed between the healthy subjects and patients with POI, and multiple signaling pathways were assessed. The TNF pathway was found to be unique in POI with classical monocytes being the major target and source of TNF signaling.
Dysfunction of cellular immunity is related to idiopathic POI. Monocytes, NK cells, and B cells, and their enriched differential genes may play a role in the development of idiopathic POI. These findings provide novel mechanistic insight for understanding the pathogenesis of POI.
摘要：
■过早卵巢功能不全（POI）是女性不孕的最常见原因之一，病因高度异质性。大多数病例是特发性的，发病机制尚不清楚。先前的研究证明，免疫系统在POI中起着至关重要的作用。然而,免疫系统的确切作用尚不清楚.本研究旨在通过单细胞RNA测序（scRNA-seq）分析POI患者外周血单个核细胞（PBMC）的特征，并探讨免疫反应在特发性POI中的潜在参与。
■从三名正常受试者和三名POI患者收集PBMC。对PBMC进行scRNA-seq以鉴定细胞簇和不同表达的基因(DEG)。进行富集分析和细胞-细胞通讯分析，以探索POI患者免疫细胞中最活跃的生物学功能。
■总共，在两组中鉴定出22个细胞簇和10种细胞类型。与正常人相比，经典单核细胞和NK细胞的百分比降低，血浆B细胞的丰度增加，和CD4/CD8比值明显高于POI。此外，IGKC的上调，IFITM1、CD69、JUND和LYZ的下调，GNLY,VCAN,和S100A9被识别，富含NK细胞介导的细胞毒性，抗原加工和呈递，和IL-17信号通路。其中,IGHM和LYZ分别是POI的所有细胞簇中最显著上调和下调的基因。健康受试者和POI患者之间的细胞间通讯强度不同，并对多个信号通路进行了评估。发现TNF途径在POI中是独特的,其中经典单核细胞是TNF信号传导的主要靶标和来源。
■细胞免疫功能异常与特发性POI有关。单核细胞,NK细胞,B细胞,它们丰富的差异基因可能在特发性POI的发生发展中起作用。这些发现为理解POI的发病机理提供了新的机制见解。
■从三名正常受试者和三名POI患者收集PBMC。对PBMC进行scRNA-seq以鉴定细胞簇和不同表达的基因(DEG)。进行富集分析和细胞-细胞通讯分析，以探索POI患者免疫细胞中最活跃的生物学功能。
■总共，在两组中鉴定出22个细胞簇和10种细胞类型。与正常人相比，经典单核细胞和NK细胞的百分比降低，血浆B细胞的丰度增加，和CD4/CD8比值明显高于POI。此外，IGKC的上调，IFITM1、CD69、JUND和LYZ的下调，GNLY,VCAN,和S100A9被识别，富含NK细胞介导的细胞毒性，抗原加工和呈递，和IL-17信号通路。其中,IGHM和LYZ分别是POI的所有细胞簇中最显著上调和下调的基因。健康受试者和POI患者之间的细胞间通讯强度不同，并对多个信号通路进行了评估。发现TNF途径在POI中是独特的,其中经典单核细胞是TNF信号传导的主要靶标和来源。
■细胞免疫功能异常与特发性POI有关。单核细胞,NK细胞,B细胞,它们丰富的差异基因可能在特发性POI的发生发展中起作用。这些发现为理解POI的发病机理提供了新的机制见解。
