Label-retaining cells of the bladder: candidate urothelial stem cells
Label-retaining cells of the bladder: candidate urothelial stem cells
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DOI：
10.1152/ajprenal.00533.2007
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发表时间：
2008-06-01
影响因子：
4.2
通讯作者：
Isseroff, Roslyn R.
中科院分区：
文献类型：
--
作者：
Kurzrock, Eric A.;Lieu, Deborah K.;Isseroff, Roslyn R.
成体组织干细胞很少复制，保留DNA核苷酸标记BrdU的时间比成熟的分裂细胞长得多，其中标记在追踪期间被稀释。这些“标记保留细胞”（LRC）已被确定为皮肤、角膜、肠和前列腺中的组织干细胞。然而，尿路中的尿路上皮干细胞尚未被发现。在这项研究中，BrdU管理确定尿路上皮LRC在大鼠膀胱与9%的上皮基底细胞保留BrdU标签1年后，其管理。其他组织中的干细胞标记物Bcl、p63、细胞角蛋白14和β 1整联蛋白免疫定位于膀胱基底上皮中或附近的尿路上皮LRC中，但不限于这些细胞。流式细胞术表明，尿路上皮LRC小，具有低粒度，并且是独特的β 4整联蛋白明亮。培养长期标记膀胱的尿路上皮细胞，发现LRC比未标记的尿路上皮细胞具有更显著的干细胞特征，即克隆形成和增殖。因此，这项工作表明，膀胱中的LRC定位于基底层，是小的、低粒度的、独特地富含β 4整联蛋白的、缓慢循环的，并且与未标记的上皮细胞相比显示出上级的克隆形成和增殖能力。我们建议，LRC代表推定的尿路上皮干细胞。
Adult tissue stem cells replicate infrequently, retaining DNA nucleotide label BrdU) for much longer periods than mature, dividing cells in which the label is diluted during a chase period. Those "labelretaining cells" (LRCs) have been identified as the tissue stem cells in skin, cornea, intestine, and prostate. However, in the urinary tract uroepithelial stem cells have not yet been identified. In this study, BrdU administration identified urothelial LRCs in the rat bladder with 9% of the epithelial basal cells retaining BrdU label 1 yr after its administration. Markers for stem cells in other tissues, Bcl, p63, cytokeratin 14, and beta 1 integrin, were immunolocalized in the basal bladder epithelium in or near urothelial LRCs, but not uniquely limited to these cells. Flow cytometry demonstrated that urothelial LRCs were small, had low granularity, and were uniquely beta 4 integrin bright. Urothelium from long-term labeled bladders was cultured and LRCs were found to be significantly more clonogenic and proliferative, characteristics of stem cells, than unlabeled urothelial cells. Thus, this work demonstrates that LRCs in the bladder localize to the basal layer, are small, low granularity, uniquely beta 4 integrin rich, slowly cycling and demonstrate superior clonogenic and proliferative ability compared with unlabeled epithelial cells. We propose that LRCs represent putative urothelial stem cells.