Yang Jun, Blum Alexander, Novak Thaddeus, Levinson Randy, Lai Eseng, Barasch Jonathan
College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Dev Biol. 2002 Jun 15;246(2):296-310. doi: 10.1006/dbio.2002.0646.
Kidney epithelia develop from the metanephric mesenchyme after receiving inductive signals from the ureteric bud and from the renal stroma. However, it is not clear how these signals induce the different types of epithelia that make up the nephron. To investigate inductive signaling, we have isolated clusters of epithelial progenitors from the metanephric mesenchyme, thereby separating them from the renal stroma. When the isolated progenitors were treated with the ureteric bud factor LIF, they expressed epithelial proteins (ZO-1, E-cadherin, laminin alpha(5)) and produced nephrons (36 glomeruli with 58 tubules), indicating that they are the target of inductive signaling from the ureteric bud, and that renal stroma is not absolutely required for epithelial development in vitro. In fact, stroma-depleted epithelial progenitors produced sevenfold more glomeruli than did intact metanephric mesenchyme (5 glomeruli, 127 tubules). Conversely, when epithelial progenitors were treated with both LIF and proteins secreted from a renal stromal cell line, glomerulogenesis was abolished but tubular epithelia were expanded (0 glomeruli, 47 tubules). Hence, by isolating epithelial progenitors from the metanephric mesenchyme, we show that they are targeted by factors from the ureteric bud and from the renal stroma, and that epithelial diversification is stimulated by the ureteric bud and limited by renal stroma.
肾上皮细胞在接受来自输尿管芽和肾基质的诱导信号后，从后肾间充质发育而来。然而，尚不清楚这些信号如何诱导构成肾单位的不同类型上皮细胞。为了研究诱导信号，我们从后肾间充质中分离出上皮祖细胞簇，从而将它们与肾基质分离。当分离出的祖细胞用输尿管芽因子白血病抑制因子（LIF）处理时，它们表达上皮蛋白（紧密连接蛋白1、E-钙黏蛋白、层粘连蛋白α5）并产生肾单位（36个肾小球和58个肾小管），这表明它们是输尿管芽诱导信号的靶标，并且肾基质对于体外上皮发育并非绝对必需。事实上，去除基质的上皮祖细胞产生的肾小球比完整的后肾间充质多七倍（5个肾小球，127个肾小管）。相反，当上皮祖细胞同时用LIF和肾基质细胞系分泌的蛋白处理时，肾小球发生被消除，但管状上皮细胞增多（0个肾小球，47个肾小管）。因此，通过从后肾间充质中分离上皮祖细胞，我们表明它们是输尿管芽和肾基质因子的靶标，并且上皮分化受输尿管芽刺激并受肾基质限制。
