轉(zhuǎn)基因‘角蛋白14-rtTA-PTR’老鼠能夠在舌上皮細(xì)胞特異性的表達(dá)角蛋白14(K14),,用強(qiáng)力霉素(Dox)處理后,也聯(lián)合表達(dá)了EGFP及顯性負(fù)性基因ΔTgfbr2,。
轉(zhuǎn)化生長(zhǎng)因子-β(transforming growth factor-β,TGF-β)對(duì)間充質(zhì)起源的細(xì)胞超刺激作用,,而對(duì)上皮或神經(jīng)外胚層來源的細(xì)胞起抑制作用。由于TGF-β信號(hào)對(duì)干細(xì)胞的周期與增殖起負(fù)調(diào)控作用,,來自中國(guó)上海交通大學(xué)的李鋒副教授對(duì)這些轉(zhuǎn)基因老鼠使用Dox誘導(dǎo)破壞了該信號(hào),,縮短了細(xì)胞周期,在較短的時(shí)間內(nèi)觀察到了那些突變細(xì)胞系的發(fā)展模式,。
他們還通過免疫組化的免疫熒光圖像,,在誘導(dǎo)的轉(zhuǎn)基因老鼠追蹤了K14+細(xì)胞。
結(jié)果表明,,從舌的尖端到后部,,這些細(xì)胞具有不同的發(fā)展模式,可能是因?yàn)檫@些細(xì)胞整合了來自微環(huán)境的位置信息,。
K14基因在舌頭及乳頭狀突起的表達(dá)是可變的,,在14+祖細(xì)胞,破壞TGF-β信號(hào)會(huì)導(dǎo)致干細(xì)胞池的增殖,。該研究表明,,舌上皮細(xì)胞的局部微環(huán)境對(duì)細(xì)胞分化提供了重要的線索。相關(guān)研究發(fā)表在4月13日的PLoS ONE,。(生物谷Deepblue編譯)
doi: 10.1371/journal.pone.0035362
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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