Single-Cell Characterization of the Frizzled 5 (Fz5) Mutant Mouse and Human Persistent Fetal Vasculature (PFV).
Single-Cell Characterization of the Frizzled 5 (Fz5) Mutant Mouse and Human Persistent Fetal Vasculature (PFV).
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DOI：
10.1167/iovs.64.3.8
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发表时间：
2023-03-01
影响因子：
4.4
通讯作者：
中科院分区：
文献类型：
--
作者：
持续性胎儿血管系统 (PFV) 是一种病理性疾病，占美国儿童失明的 4.8%。然而，人们对 PFV 细胞组成和发病机制知之甚少。本研究旨在表征PFV细胞组成和相关分子特征，并试图为进一步了解该疾病奠定基础。进行免疫组织化学以在组织水平表征细胞类型。对产后两个早期年龄的正常小鼠和 Fz5 突变小鼠的玻璃体细胞以及人类 PFV 样本进行单细胞 RNA 测序 (sc-RNAseq)。使用生物信息学工具对细胞进行聚类并分析其分子特征和功能。本研究的结果如下：（1）通过sc-RNAseq和免疫组织化学对玻璃体血管系统和PFV中总共10种确定的和一种未确定的细胞类型进行了表征； (2)突变型PFV中特异保留了神经嵴来源的黑素细胞、星形胶质细胞和成纤维细胞； (3) Fz5突变体在出生后3岁时被发现拥有更多的玻璃体细胞，但在出生后6岁时恢复到与野生型相似的水平； (4)在突变玻璃体中检测到吞噬和增殖环境以及细胞间相互作用的改变； （5）人PFV样本与小鼠具有相同的成纤维细胞、内皮细胞和巨噬细胞类型，但具有不同的免疫细胞，包括T细胞、NK细胞和中性粒细胞；最后，（6）某些小鼠和人类玻璃体细胞类型之间也有一些神经嵴特征。我们对 Fz5 突变小鼠和两个人类 PFV 样本中的 PFV 细胞组成和相关分子特征进行了表征。过度迁移的玻璃体细胞、这些细胞的内在分子特性、吞噬环境和细胞间相互作用可能共同促成 PFV 的发病机制。人类 PFV 与小鼠具有某些相同的细胞类型和分子特征。
Persistent fetal vasculature (PFV) is a pathological condition accounting for 4.8% of children's blindness in the United States. However, the PFV cell composition and pathogenetic mechanisms are poorly understood. This study aims to characterize PFV cell composition and associated molecular features and attempts to lay a foundation for further understanding the disease. Immunohistochemistry was conducted to characterize cell types at the tissue level. Single-cell RNA sequencing (sc-RNAseq) was performed on the vitreous cells derived from normal and Fz5 mutant mice at two early postnatal ages and human PFV samples. Bioinformatic tools were used to cluster cells and analyze their molecular features and functions. The findings of this study are as follows: (1) a total of 10 defined and one undefined cell types were characterized in both the hyaloid vessel system and PFV by sc-RNAseq and immunohistochemistry; (2) neural crest-derived melanocytes, astrocytes, and fibroblasts were specifically retained in the mutant PFV; (3) Fz5 mutants were found to possess more vitreous cells at early postnatal age 3 but returned to similar levels as the wild type at postnatal age 6; (4) altered phagocytic and proliferation environments and cell-cell interactions were detected in the mutant vitreous; (5) the human PFV samples shared fibroblast, endothelial and macrophage cell types with the mouse, but having distinct immune cells including T cells, NK cells and Neutrophils; and last, (6) some neural crest features were also shared between certain mouse and human vitreous cell types. We characterized PFV cell composition and associated molecular features in the Fz5 mutant mice and two human PFV samples. The excessively migrated vitreous cells, intrinsic molecular properties of these cells, phagocytic environment, and cell-cell interactions may together contribute to PFV pathogenesis. Human PFV shares certain cell types and molecular features with the mouse.
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影响因子：
5.3
作者：
Klopstein, Armelle;Santos-Nogueira, Eva;Lopez-Vales, Ruben
通讯作者：
Lopez-Vales, Ruben
影响因子：
14.8
作者：
Efremova, Mirjana;Vento-Tormo, Miquel;Vento-Tormo, Roser
通讯作者：
Vento-Tormo, Roser
影响因子：
5.4
作者：
BARANKIEWICZ, J;COHEN, A
通讯作者：
COHEN, A
影响因子：
4
作者：
Goupille, Olivier;Pallafacchina, Giorgia;Buckingham, Margaret
通讯作者：
Buckingham, Margaret
影响因子：
2.5
作者：
Kulesa, P;Ellies, DL;Trainor, PA
通讯作者：
Trainor, PA