转基因‘角蛋白14-rtTA-PTR’老鼠能够在舌上皮细胞特异性的表达角蛋白14(K14)，用强力霉素(Dox)处理后，也联合表达了EGFP及显性负性基因ΔTgfbr2。
转化生长因子-β（transforming growth factor-β,TGF-β)对间充质起源的细胞超刺激作用，而对上皮或神经外胚层来源的细胞起抑制作用。由于TGF-β信号对干细胞的周期与增殖起负调控作用，来自中国上海交通大学的李锋副教授对这些转基因老鼠使用Dox诱导破坏了该信号，缩短了细胞周期，在较短的时间内观察到了那些突变细胞系的发展模式。
他们还通过免疫组化的免疫荧光图像，在诱导的转基因老鼠追踪了K14+细胞。
结果表明，从舌的尖端到后部，这些细胞具有不同的发展模式，可能是因为这些细胞整合了来自微环境的位置信息。
K14基因在舌头及乳头状突起的表达是可变的，在14+祖细胞，破坏TGF-β信号会导致干细胞池的增殖。该研究表明，舌上皮细胞的局部微环境对细胞分化提供了重要的线索。相关研究发表在4月13日的PLoS ONE。（生物谷Deepblue编译）
doi: 10.1371/journal.pone.0035362
PMC:
PMID:
Local Microenvironment Provides Important Cues for Cell Differentiation in Lingual Epithelia
Feng Li, Mingliang Zhou.
TTransgenic Keratin14-rtTA-PTR mice specifically express Keratin14 (K14) in the tongue epithelia, as well as co-express EGFP and the dominant negative ΔTgfbr2 genes upon treatment with Doxycycline (Dox).As TGF-β signaling negatively regulates the stem cell cycle and proliferation, its disruption by Dox induction in these transgenic mice shortens the cell cycle and allows observation of the final fate of those mutated cell lineages within a short period of time.Here, we used inducible transgenic mice to track the K14+ cells through the cell migration stream by immunohistochemical an immunofluorescent imaging.We showed that these cells have different development patterns from the tip to posterior of the tongue, achieved presumably by integrating positional information from the microenvironment.The expression of the K14 gene was variable, depending on the location of the tongue and papillae.Disruption of TGF-β signaling in K14+ progenitor cells resulted in proliferation of stem cell pools
