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摘要 : 本期封面所示为一个完整肾脏细胞器的拼接式免疫荧光扫描图,它显示了其结构的复杂性,实际尺寸为5.7 mm × 6.4 mm。胚胎中人类肾脏的发育依赖于两种不同的干细胞类型:一种生成收集管,另一种生成功能性肾单位。


本期封面所示为一个完整肾脏细胞器的拼接式免疫荧光扫描图,它显示了其结构的复杂性,实际尺寸为5.7 mm × 6.4 mm。胚胎中人类肾脏的发育依赖于两种不同的干细胞类型:一种生成收集管,另一种生成功能性肾单位。Melissa Little、Minoru Takasato及同事以前发现, “人多能干细胞”(hPSCs)能分化成这两种类型的祖细胞。他们现在识别出了不仅诱导这些结构、而且诱导周围细胞类型(包括小间隙和血管)所需的信号条件。采用这种方法,他们培养出了能重现胚胎肾脏的功能区域化的肾脏细胞器。这些细胞器中所达到的组织复杂性和功能化程度还不能与一个正常的肾脏相比,但与正常的人类胚胎肾脏相同。重要的是,它们提供了证明自己在药物毒性筛选、在模拟遗传性肾病方面所具有潜力的证据,或许还为细胞疗法提供了特定的肾脏细胞类型。封面图片: Minoru Takasato


Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis


The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells1. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.

来源: Nature 浏览次数:0


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