本期封面所示為一個(gè)完整腎臟細(xì)胞器的拼接式免疫熒光掃描圖，它顯示了其結(jié)構(gòu)的復(fù)雜性，實(shí)際尺寸為5.7 mm ? 6.4 mm。胚胎中人類(lèi)腎臟的發(fā)育依賴(lài)于兩種不同的干細(xì)胞類(lèi)型：一種生成收集管，另一種生成功能性腎單位。Melissa Little、Minoru Takasato及同事以前發(fā)現(xiàn)， “人多能干細(xì)胞”(hPSCs)能分化成這兩種類(lèi)型的祖細(xì)胞。他們現(xiàn)在識(shí)別出了不僅誘導(dǎo)這些結(jié)構(gòu)、而且誘導(dǎo)周?chē)?xì)胞類(lèi)型(包括小間隙和血管)所需的信號(hào)條件。采用這種方法，他們培養(yǎng)出了能重現(xiàn)胚胎腎臟的功能區(qū)域化的腎臟細(xì)胞器。這些細(xì)胞器中所達(dá)到的組織復(fù)雜性和功能化程度還不能與一個(gè)正常的腎臟相比，但與正常的人類(lèi)胚胎腎臟相同。重要的是，它們提供了證明自己在藥物毒性篩選、在模擬遺傳性腎病方面所具有潛力的證據(jù)，或許還為細(xì)胞療法提供了特定的腎臟細(xì)胞類(lèi)型。封面圖片: Minoru Takasato
原文鏈接：
Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis
原文摘要：
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.
