Potten Christopher S, Booth Catherine, Tudor Gregory L, Booth Dawn, Brady Gerard, Hurley Patricia, Ashton Gary, Clarke Robert, Sakakibara Shin-ichi, Okano Hideyuki
Epithelial Biology Department, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK.
Differentiation. 2003 Jan;71(1):28-41. doi: 10.1046/j.1432-0436.2003.700603.x.
There are few reliable markers for adult stem cells and none for those of the intestinal epithelium. Previously, indirect experimental approaches have predicted stem cell position and numbers. The Musashi-1 (Msi-1) gene encodes an RNA binding protein associated with asymmetric divisions in neural progenitor cells. Two-day-old, adult, and 4.5 h, 1-, 2-, 4- and 12-day post-irradiation samples of BDF1 mouse small intestine, together with some samples of mouse colon were stained with a rat monoclonal antibody to Musashi-1 (14 H-1). Min ( + / - ) mice with small intestinal adenomas of varying sizes were also analysed. Samples of human small and large bowel were also studied but the antibody staining was weak. Musashi-1 expression was observed using immunohistochemistry in neonatal, adult, and regenerating crypts with a staining pattern consistent with the predicted number and distribution of early lineage cells including the functional stem cells in these situations. Early dysplastic crypts and adenomas were also strongly Musashi-1 positive. In situ hybridization studies showed similar expression patterns for the Musashi mRNA and real-time quantitative RT-PCR showed dramatically more Msi-1 mRNA expression in Min tumours compared with adjacent normal tissue. These observations suggest that Musashi-1 is a marker of stem and early lineage progenitor cells in murine intestinal tissue.
目前几乎没有可靠的成体干细胞标志物，而肠道上皮干细胞的标志物则完全没有。此前，间接实验方法已对干细胞的位置和数量进行了预测。Musashi-1（Msi-1）基因编码一种与神经祖细胞不对称分裂相关的RNA结合蛋白。用抗Musashi-1的大鼠单克隆抗体（14 H-1）对BDF1小鼠小肠的2日龄、成年以及照射后4.5小时、1天、2天、4天和12天的样本，以及一些小鼠结肠样本进行染色。还对患有不同大小小肠腺瘤的Min（+/-）小鼠进行了分析。也对人类小肠和大肠样本进行了研究，但抗体染色较弱。通过免疫组织化学在新生、成年和再生隐窝中观察到Musashi-1的表达，其染色模式与这些情况下包括功能性干细胞在内的早期谱系细胞的预测数量和分布一致。早期发育异常隐窝和腺瘤也呈强烈的Musashi-1阳性。原位杂交研究显示Musashi mRNA具有相似的表达模式，实时定量RT-PCR显示与相邻正常组织相比，Min肿瘤中的Msi-1 mRNA表达显著增加。这些观察结果表明，Musashi-1是小鼠肠道组织中干细胞和早期谱系祖细胞的标志物。
