Production of vascularised kidney organoids with anatomically appropriate tubular organization and connection, solely from embryonic stem cells

Organoids generated from pluripotent stem cells typically possess accurate micro anatomy but lack the higher order organization of an organ, which limits how well they mimic real organs. In this study we present a method for engineering kidney organoids solely from mouse embryonic stem cells (mESC), with much improved higher-order anatomy. mESC were differentiated to ureteric bud (iUB), nephron (iNP) and stromal lineages (iSP); pure progenitor populations were sorted and their expression profiles were compared to their embryonic day (E) 11.5 and 12.5 counterpart. Results: Comparative analysis showed the similarity of iUB progenitors to both E11.5 and E12.5 UB cells. However, both iNP and iSP were distinct from their ex-fetu counterparts. Overall design: RNA profiles of the iUB, iNP, and iSP were compared to that of the E11.5 and E12.5 equivalant. 36 samples were included and are divided into nine groups (each group has four different repeats)

由多能干细胞（pluripotent stem cells）诱导产生的类器官（organoids）通常具备精准的微观解剖结构，但缺乏完整器官的高阶组织结构，这极大限制了其模拟真实器官的能力。本研究报道了一种仅使用小鼠胚胎干细胞（mouse embryonic stem cells, mESC）构建肾脏类器官的方法，可显著优化其高阶解剖结构。将mESC定向分化为输尿管芽（ureteric bud, iUB）、肾单位（nephron, iNP）与基质谱系（stromal lineages, iSP）；分选获得纯化的祖细胞群后，将其表达谱与胚胎日（embryonic day, E）11.5及12.5期的对应细胞进行比对。结果：比较分析表明，iUB祖细胞与E11.5、E12.5期的UB细胞均具有较高相似性；但iNP与iSP细胞均与其离体胚胎来源的对应细胞存在显著差异。实验设计：将iUB、iNP及iSP的RNA表达谱与E11.5和E12.5期的对应细胞进行对比分析。本研究共纳入36份样本，分为9组，每组设置4次生物学重复。