Department of Medicine, Huddinge, Karolinska Institutet, Solna, Sweden.
Department of Immunology, Genetics, and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neuro-injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
Stem Cell Reports. 2022 May 10;17(5):1089-1104. doi: 10.1016/j.stemcr.2022.03.016. Epub 2022 Apr 21.
Humanized mouse models and mouse-adapted SARS-CoV-2 virus are increasingly used to study COVID-19 pathogenesis, so it is important to learn where the SARS-CoV-2 receptor ACE2 is expressed. Here we mapped ACE2 expression during mouse postnatal development and in adulthood. Pericytes in the CNS, heart, and pancreas express ACE2 strongly, as do perineurial and adrenal fibroblasts, whereas endothelial cells do not at any location analyzed. In a number of other organs, pericytes do not express ACE2, including in the lung where ACE2 instead is expressed in bronchial epithelium and alveolar type II cells. The onset of ACE2 expression is organ specific: in bronchial epithelium already at birth, in brain pericytes before, and in heart pericytes after postnatal day 10.5. Establishing the vascular localization of ACE2 expression is central to correctly interpret data from modeling COVID-19 in the mouse and may shed light on the cause of vascular COVID-19 complications.
人源化小鼠模型和适应小鼠的 SARS-CoV-2 病毒越来越多地被用于研究 COVID-19 的发病机制,因此了解 SARS-CoV-2 受体 ACE2 的表达位置非常重要。在这里,我们绘制了 ACE2 在小鼠出生后发育和成年期的表达图谱。CNS、心脏和胰腺中的周细胞强烈表达 ACE2,神经外膜和成肾上腺成纤维细胞也是如此,而在任何分析的位置内皮细胞均不表达 ACE2。在许多其他器官中,周细胞不表达 ACE2,包括肺,其中 ACE2 则在支气管上皮细胞和肺泡 II 型细胞中表达。ACE2 的表达起始具有器官特异性:在支气管上皮细胞中出生时即有表达,在脑周细胞中则在出生后第 10.5 天之前表达,在心周细胞中则在之后表达。确定 ACE2 表达的血管定位对于正确解释在小鼠中模拟 COVID-19 的数据至关重要,并且可能揭示血管 COVID-19 并发症的原因。