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使用 scRNA-seq 鉴定正常和输卵管积水疾病状态下人类输卵管的细胞异质性。

Cellular heterogeneity of human fallopian tubes in normal and hydrosalpinx disease states identified using scRNA-seq.

机构信息

Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.

Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.

出版信息

Dev Cell. 2022 Apr 11;57(7):914-929.e7. doi: 10.1016/j.devcel.2022.02.017. Epub 2022 Mar 22.

Abstract

Fallopian tube (FT) homeostasis requires dynamic regulation of heterogeneous cell populations and is disrupted in infertility and ovarian cancer. Here, we applied single-cell RNA-seq to profile 59,738 FT cells from four healthy, pre-menopausal subjects. The resulting cell atlas contains 12 major cell types representing epithelial, stromal, and immune compartments. Re-clustering of epithelial cells identified four ciliated and six non-ciliated secretory epithelial subtypes, two of which represent potential progenitor pools: one leading to mature secretory cells and the other contributing to either ciliated cells or one of the stromal cell types. To understand how FT cell numbers and states change in a disease state, we analyzed 17,798 cells from two hydrosalpinx samples and observed shifts in epithelial and stromal populations and cell-type-specific changes in extracellular matrix and TGF-β signaling; this underscores fibrosis pathophysiology. This resource is expected to facilitate future studies aimed at expanding understanding of fallopian tube homeostasis in normal development and disease.

摘要

输卵管(FT)的稳态需要异质性细胞群体的动态调节,而这一过程在不孕和卵巢癌中被打乱。在这里,我们应用单细胞 RNA 测序对来自四个健康、绝经前的个体的 59738 个 FT 细胞进行了分析。由此产生的细胞图谱包含了代表上皮、基质和免疫区室的 12 种主要细胞类型。对上皮细胞的重新聚类鉴定出了四个纤毛和六个非纤毛分泌上皮亚型,其中两个代表潜在的祖细胞池:一个导致成熟的分泌细胞,另一个则导致纤毛细胞或基质细胞类型之一。为了了解在疾病状态下 FT 细胞数量和状态如何变化,我们分析了两个积水性输卵管样本中的 17798 个细胞,观察到上皮和基质群体的转移以及细胞类型特异性的细胞外基质和 TGF-β 信号的变化;这突出了纤维化的病理生理学。这个资源预计将有助于未来的研究,旨在扩大对正常发育和疾病中输卵管稳态的理解。

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