Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium
Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium
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DOI：
10.1152/ajpgi.00004.2009
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发表时间：
2009-05-01
影响因子：
4.5
通讯作者：
Magness, Scott T.
中科院分区：
文献类型：
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作者：
Formeister, Eric J.;Sionas, Ayn L.;Magness, Scott T.
福梅斯特 EJ、西奥纳斯 AL、洛兰斯 DK、巴克利 CL、李 GH、马格尼斯 ST。不同的 SOX9 水平对小肠上皮的干细胞/祖细胞群和肠内分泌细胞进行差异标记。 Am J Physiol Gastrointest Liver Physiol 296：G1108-G1118，2009。首次发表于 2009 年 2 月 19 日； doi:10.1152/ajpgi.00004.2009.-SOX转录因子具有以剂量依赖性方式调节干/祖细胞增殖和分化的能力。 SOX9 在小肠上皮干细胞区表达。因此，我们假设 SOX9 可能存在差异水平，影响小肠上皮的增殖和/或分化。使用 Sox9 增强型绿色荧光蛋白 (Sox9(EGFP)) 转基因小鼠研究小肠中的 Sox9 表达水平。 Sox9(EGFP) 水平与内源性 SOX9 水平相关，内源性 SOX9 水平以两个稳态水平表达，称为 Sox9(EGFPLO) 和 Sox9(EGFPHI)。基于隐窝的柱状细胞是 Sox9(EGFPLO)，并且表现出干细胞标记物 Lgr5 的富集表达。 Sox9(EGFPHI)细胞表达嗜铬粒蛋白A和P物质，但不表达Ki67和神经原素3，表明Sox9(EGFPHI)细胞是有丝分裂后肠内分泌细胞。 SOX9 在隐窝细胞系中的过度表达会停止增殖并诱导形态变化。这些数据支持 SOX9 在肠上皮中的双峰作用，其中低 SOX9 表达支持增殖能力，高 SOX9 表达抑制增殖。
Formeister EJ, Sionas AL, Lorance DK, Barkley CL, Lee GH, Magness ST. Distinct SOX9 levels differentially mark stem/progenitor populations and enteroendocrine cells of the small intestine epithelium. Am J Physiol Gastrointest Liver Physiol 296: G1108-G1118, 2009. First published February 19, 2009; doi:10.1152/ajpgi.00004.2009.-SOX transcription factors have the capacity to modulate stem/progenitor cell proliferation and differentiation in a dose-dependent manner. SOX9 is expressed in the small intestine epithelial stem cell zone. Therefore, we hypothesized that differential levels of SOX9 may exist, influencing proliferation and/or differentiation of the small intestine epithelium. Sox9 expression levels in the small intestine were investigated using a Sox9 enhanced green fluorescent protein (Sox9(EGFP)) transgenic mouse. Sox9(EGFP) levels correlate with endogenous SOX9 levels, which are expressed at two steady-state levels, termed Sox9(EGFPLO) and Sox9(EGFPHI). Crypt-based columnar cells are Sox9(EGFPLO) and demonstrate enriched expression of the stem cell marker, Lgr5. Sox9(EGFPHI) cells express chromogranin A and substance P but do not express Ki67 and neurogenin3, indicating that Sox9(EGFPHI) cells are postmitotic enteroendocrine cells. Overexpression of SOX9 in a crypt cell line stopped proliferation and induced morphological changes. These data support a bimodal role for SOX9 in the intestinal epithelium, where low SOX9 expression supports proliferative capacity, and high SOX9 expression suppresses proliferation.