小柯机器人

德国亚琛工业大学Rafael Kramann团队近期取得重要工作进展，他们研究发现起源于CD24⁺细胞的成人肾脏类器官可以作为成人多囊肾病的高级模型。相关研究工作2022年10月27日在线发表于《自然—遗传学》杂志上。

研究人员发现肾小管起源于一个独特的CD24⁺上皮亚群。长期培养的CD24⁺细胞来源的肾小管表现出人肾小管的功能性特征。研究人员表明，肾小管可以用来模拟最常见的遗传性肾脏疾病，即常染色体显性多囊肾（ADPKD），重组这种疾病的表型特征与囊肿形成。CRISPR-Cas9基因编辑的PKD1和PKD2基因敲除的肾小管和人类ADPKD及对照组织的单细胞RNA测序显示疾病驱动基因上调的相似性。

此外，在一项概念证明中，研究人员证明了tolvaptan（唯一被批准用于治疗ADPKD的药物）对小管样囊肿的大小有显著影响，但对多能干细胞来源的模型无影响。因此，肾小管来源于管状上皮亚群，代表了先进的ADPKD疾病建模系统。

据介绍，成人肾脏器官被描述为严格的管状上皮细胞，并被称为肾小管。目前，肾小管形成的细胞来源还不是很清楚。

附：英文原文

Title: Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease

Author: Xu, Yaoxian, Kuppe, Christoph, Perales-Patn, Javier, Hayat, Sikander, Kranz, Jennifer, Abdallah, Ali T., Nagai, James, Li, Zhijian, Peisker, Fabian, Saritas, Turgay, Halder, Maurice, Menzel, Sylvia, Hoeft, Konrad, Kenter, Annegien, Kim, Hyojin, van Roeyen, Claudia R. C., Lehrke, Michael, Moellmann, Julia, Speer, Thimoteus, Buhl, Eva M., Hoogenboezem, Remco, Boor, Peter, Jansen, Jitske, Knopp, Cordula, Kurth, Ingo, Smeets, Bart, Bindels, Eric, Reinders, Marlies E. J., Baan, Carla, Gribnau, Joost, Hoorn, Ewout J., Steffens, Joachim, Huber, Tobias B., Costa, Ivan, Floege, Jrgen, Schneider, Rebekka K., Saez-Rodriguez, Julio, Freedman, Benjamin S., Kramann, Rafael

Issue&Volume: 2022-10-27

Abstract: Adult kidney organoids have been described as strictly tubular epithelia and termed tubuloids. While the cellular origin of tubuloids has remained elusive, here we report that they originate from a distinct CD24+ epithelial subpopulation. Long-term-cultured CD24+ cell-derived tubuloids represent a functional human kidney tubule. We show that kidney tubuloids can be used to model the most common inherited kidney disease, namely autosomal dominant polycystic kidney disease (ADPKD), reconstituting the phenotypic hallmark of this disease with cyst formation. Single-cell RNA sequencing of CRISPR–Cas9 gene-edited PKD1- and PKD2-knockout tubuloids and human ADPKD and control tissue shows similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, has a significant effect on cyst size in tubuloids but no effect on a pluripotent stem cell-derived model. Thus, tubuloids are derived from a tubular epithelial subpopulation and represent an advanced system for ADPKD disease modeling.

DOI: 10.1038/s41588-022-01202-z

Source: https://www.nature.com/articles/s41588-022-01202-z

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex