FATE OF BF 2 EXPRESSING RENAL PROGENITORS

描述：病变肾脏中活化基质细胞的起源， 这些细胞在诱发终末期肾病中所起的作用仍然存在 难以捉摸，这个棘手的临床问题很难解决，因为 正常肾脏间质的起源、分化和功能 仍然知之甚少。我们发现，有翼障碍转录因子， BF-2由肾间质祖细胞选择性表达， 表达基质祖细胞对于肾上皮生长是必需的， 分化在本研究中，我们将利用BF-2 mRNA作为分子标记， 以鉴定肾间质祖细胞并检验描述肾间质祖细胞的假设。 起源，分化，和这个细胞群体的命运。具体目标1、 通过逆转录病毒介导的基因转染， 转移谱系追踪技术。血统标记的差异化命运， 将表征存在于早期鸡胚中的BF-2表达细胞 通过形态学和分子标记分析。Specific Aim 2将探测BF-2 功能和细胞过程受到BF 2缺失的干扰。我们展示BF-2 空基质细胞经历早熟分化，而对照细胞 BF-2表达下调与分化一致。我们将 确定腺病毒介导的组成型高水平BF-2表达 延迟体外基质分化。我们将检验这个假设， BF-2缺失引起的早熟分化扰乱了 调控输尿管芽生长的基质因子的表达模式。数据 产生的将为未来的研究提供基础上的起源激活 病肾间质细胞及其在肾单位变性中的作用 和/或修复。

DESCRIPTION: The origin of activated stromal cells in the diseased kidney and the role that these cells play in precipitating end stage renal disease remains elusive, This recalcitrant clinical problem is difficult to address since the origin, differentiation and function of renal stroma in the healthy kidney remains poorly understood. We show that the Winged Helix transcription factor, BF-2, is selectively expressed by renal stromal progenitors and that BF-2 expressing stromal progenitors are essential for renal epithelial growth and differentiation. In this proposal we will use BF-2 mRNA as a molecular marker to identify renal stromal progenitors and test hypotheses describing the origin, differentiation, and fate of this cell population. In Specific Aim 1, the origin of renal stromal cells will be analyzed by retroviral mediated gene transfer lineage tracing techniques. The differentiated fate of lineage tagged, BF-2 expressing cells present in the early chick embryo will be characterized by morphological and molecular marker analyses. Specific Aim 2 will probe BF-2 function and the cellular processes perturbed by BF2 deletion. We show BF-2 null stromal cells undergo precocious differentiation while control cells down-regulate BF-2 expression coincident with differentiation. We will determine if adenovirus mediated constitutive, high level BF-2 expression delays stromal differentiation in vitro. We will test the hypothesis that precocious differentiation caused by BF-2 deletion perturbs the temporal expression patterns of stromal factors regulating ureteric bud growth. Data generated will provide the basis for future studies on the origin of activated stromal cells in the diseased kidney and their role in nephron degeneration and/or repair.