Onoda Naoki, Kawabata Ayako, Hasegawa Kumi, Sakakura Megumi, Urakawa Itaru, Seki Masahide, Zenkoh Junko, Suzuki Ayako, Suzuki Yutaka
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa-shi, Chiba 277-0882, Japan.
Research Core Function Laboratories, Research Unit, R&D Division, Kyowa Kirin Co., Ltd., Machida-shi, Tokyo 194-8533, Japan.
DNA Res. 2022 Feb 27;29(2). doi: 10.1093/dnares/dsac007.
The kidney is a complex organ that consists of various types of cells. It is occasionally difficult to resolve molecular alterations and possible perturbations that the kidney experiences due to drug-induced damage. In this study, we performed spatial and single-cell transcriptome analysis of rat kidneys and constructed a precise rat renal cell atlas with spatial information. Using the constructed catalogue, we were able to characterize cells of several minor populations, such as macula densa or juxtaglomerular cells. Further inspection of the spatial gene expression data allowed us to identify the upregulation of genes involved in the renin regulating pathway in losartan-treated populations. Losartan is an angiotensin II receptor antagonist drug, and the observed upregulation of the renin pathway-related genes could be due to feedback from the hypotensive action of the drug. Furthermore, we found spatial heterogeneity in the response to losartan among the glomeruli. These results collectively indicate that integrated single-cell and spatial gene expression analysis is a powerful approach to reveal the detailed associations between the different cell types spanning the complicated renal compartments.
肾脏是一个由多种类型细胞组成的复杂器官。由于药物诱导的损伤，肾脏所经历的分子改变和可能的扰动有时难以解析。在本研究中，我们对大鼠肾脏进行了空间和单细胞转录组分析，并构建了具有空间信息的精确大鼠肾细胞图谱。利用构建的图谱，我们能够鉴定几个少数细胞群体的细胞，如致密斑或球旁细胞。对空间基因表达数据的进一步检查使我们能够确定在氯沙坦处理群体中肾素调节途径相关基因的上调。氯沙坦是一种血管紧张素II受体拮抗剂药物，观察到的肾素途径相关基因的上调可能是由于该药物降压作用的反馈。此外，我们发现肾小球对氯沙坦的反应存在空间异质性。这些结果共同表明，整合单细胞和空间基因表达分析是揭示跨越复杂肾区室的不同细胞类型之间详细关联的有力方法。
