Cloning and variation of adult renal tubular progenitors

Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that renal progenitor cells can be cloned from renal needle biopsy sample of CKD patients. Progenitor cells can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture. Overall design: Tissue sample from CKD patients, isolated human Sox9+ renal tubular progenitors, and in vitro differentiated kidney organoids were prepared for RNA-sequencing. Duplicate experiments were taken from 2 biological samples.

肾脏损伤表现为肾小管与肾小球系统进行性且不可逆转的破坏。然而临床研究证实，存活的急性肾损伤（AKI）患者往往可恢复肾脏结构与功能。相应地，既往研究表明，小鼠在遭受严重肾损伤后可出现肾小管再生，并将小鼠Sox9+肾祖细胞与该再生过程关联起来。本研究证实，可从慢性肾脏病（CKD）患者的肾脏穿刺活检样本中克隆获得肾祖细胞；在三维培养体系中，此类祖细胞可自发组装为表达近端/远端肾小管细胞标志物的肾脏类器官。
实验整体设计：采集慢性肾脏病（CKD）患者的组织样本、分离人源Sox9+肾管状祖细胞，并制备体外分化的肾脏类器官，以上三类样本均用于RNA测序（RNA-sequencing）；实验设置重复，且重复实验以2份生物学样本为基础开展。