Mesh : Humans Nasolacrimal Duct / metabolism Lacrimal Duct Obstruction / genetics metabolism Single-Cell Gene Expression Analysis Dacryocystorhinostomy / adverse effects methods Inflammation / metabolism Lacrimal Apparatus / metabolism

来  源:   DOI:10.1167/iovs.65.3.38   PDF(Pubmed)

Abstract:
UNASSIGNED: The aim of this study was to describe the transcriptional changes of individual cellular components in the lacrimal sac in patients with primary acquired nasolacrimal duct obstruction (PANDO) and attempt to construct the first lacrimal sac cellular atlas to elucidate the potential mechanisms that may drive the disease pathogenesis.
UNASSIGNED: Lacrimal sac samples were obtained intra-operatively during the endoscopic dacryocystorhinostomy (EnDCR) procedure from five patients. Single-cell RNA sequencing was performed to analyze each individual cell population including epithelial and immune cells during the early inflammatory and late inflammatory phases of the disease.
UNASSIGNED: Eleven cell types were identified among 25,791 cells. T cells and B cells were the cell populations with the greatest variation in cell numbers between the two phases and were involved in immune response and epithelium migration-related pathways. The present study showed that epithelial cells highly expressed the genes of senescence-associated secretory phenotype (SASP) and were involved in influencing the inflammation, neutrophil chemotaxis, and migration during the late inflammatory stage. Enhanced activity of CXCLs-CXCRs between the epithelial cells and neutrophils was noted by the cell-cell communication analysis and is suspected to play a role in inflammation by recruiting more neutrophils.
UNASSIGNED: The study presents a comprehensive single-cell landscape of the lacrimal sac cells in different phases of PANDO. The contribution of T cells, B cells, and epithelial cells to the inflammatory response, and construction of the intercellular signaling networks between the cells within the lacrimal sac has further enhanced the present understanding of the PANDO pathogenesis.
摘要:
这项研究的目的是描述原发性获得性鼻泪管阻塞(PANDO)患者泪囊中单个细胞成分的转录变化,并试图构建第一个泪囊细胞图谱以阐明可能驱动疾病发病机理的潜在机制。
在内窥镜泪囊鼻腔造口术(EnDCR)过程中,从五名患者的术中获取泪囊样本。进行单细胞RNA测序以分析在疾病的早期炎症阶段和晚期炎症阶段的每个单独的细胞群,包括上皮细胞和免疫细胞。
在25,791个细胞中鉴定出11种细胞类型。T细胞和B细胞是两个阶段之间细胞数量变化最大的细胞群体,并参与免疫反应和上皮迁移相关途径。本研究表明,上皮细胞高表达衰老相关分泌表型(SASP)基因,并参与影响炎症,中性粒细胞趋化性,并在炎症晚期迁移。细胞-细胞通讯分析注意到上皮细胞和嗜中性粒细胞之间CXCLs-CXCRs的活性增强,并怀疑通过招募更多的嗜中性粒细胞在炎症中起作用。
该研究提出了PANDO不同阶段的泪囊细胞的全面单细胞景观。T细胞的贡献,B细胞,和上皮细胞的炎症反应,泪囊内细胞之间的细胞间信号网络的构建进一步增强了目前对PANDO发病机制的理解。
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