Division of Developmental Biology, Cincinnati Children's Hospital Medical Center and the University of Cincinnati School of Medicine, Cincinnati, Ohio, United States of America.
PLoS One. 2011;6(9):e24640. doi: 10.1371/journal.pone.0024640. Epub 2011 Sep 8.
The podocyte is a remarkable cell type, which encases the capillaries of the kidney glomerulus. Although mesodermal in origin it sends out axonal like projections that wrap around the capillaries. These extend yet finer projections, the foot processes, which interdigitate, leaving between them the slit diaphragms, through which the glomerular filtrate must pass. The podocytes are a subject of keen interest because of their key roles in kidney development and disease.
METHODOLOGY/PRINCIPAL FINDINGS: In this report we identified and characterized a novel transgenic mouse line, MafB-GFP, which specifically marked the kidney podocytes from a very early stage of development. These mice were then used to facilitate the fluorescent activated cell sorting based purification of podocytes from embryos at E13.5 and E15.5, as well as adults. Microarrays were then used to globally define the gene expression states of podocytes at these different developmental stages. A remarkable picture emerged, identifying the multiple sets of genes that establish the neuronal, muscle, and phagocytic properties of podocytes. The complete combinatorial code of transcription factors that create the podocyte was characterized, and the global lists of growth factors and receptors they express were defined.
CONCLUSIONS/SIGNIFICANCE: The complete molecular character of the in vivo podocyte is established for the first time. The active molecular functions and biological processes further define their unique combination of features. The results provide a resource atlas of gene expression patterns of developing and adult podocytes that will help to guide further research of these incredible cells.
足细胞是一种特殊的细胞类型,包裹着肾脏肾小球的毛细血管。虽然它起源于中胚层,但它会发出类似于轴突的突起,包裹在毛细血管周围。这些突起进一步延伸出更细的突起,即足突,它们相互交错,在它们之间留下了裂隙隔膜,肾小球滤过液必须通过这些隔膜。足细胞是一个非常有趣的研究对象,因为它们在肾脏发育和疾病中起着关键作用。
方法/主要发现:在本报告中,我们鉴定并描述了一种新型的转基因小鼠品系 MafB-GFP,该品系能够特异性标记肾脏足细胞从发育的早期阶段。然后,这些小鼠被用于通过荧光激活细胞分选从 E13.5 和 E15.5 胚胎以及成年小鼠中纯化足细胞。然后使用微阵列全局定义这些不同发育阶段的足细胞的基因表达状态。一个显著的结果出现了,确定了建立足细胞神经元、肌肉和吞噬特性的多组基因。创建足细胞的转录因子的完整组合代码被表征,并且定义了它们表达的生长因子和受体的全局列表。
结论/意义:首次建立了体内足细胞的完整分子特征。其主动的分子功能和生物学过程进一步定义了它们独特的特征组合。这些结果提供了一个发育中和成年足细胞基因表达模式的资源图谱,将有助于指导对这些令人难以置信的细胞的进一步研究。