歐洲研究人員13日在英國《自然－細(xì)胞生物學(xué)》雜志網(wǎng)絡(luò)版上發(fā)表報(bào)告說,，他們發(fā)現(xiàn)兩種蛋白質(zhì)能控制皮膚干細(xì)胞轉(zhuǎn)化成皮膚細(xì)胞,。這一發(fā)現(xiàn)將有助于研究人員更好地了解皮膚生成機(jī)理及皮膚癌的致病原因等。
歐洲分子生物實(shí)驗(yàn)室的研究人員通過動(dòng)物實(shí)驗(yàn)發(fā)現(xiàn),，蛋白質(zhì)C／EBPα和C／EBPβ在控制皮膚干細(xì)胞何時(shí)停止增殖,、何時(shí)開始分化成皮膚細(xì)胞的過程中發(fā)揮著重要作用,。
研究人員隨后利用基因工程技術(shù)培育出身體不攜帶C／EBPα和C／EBPβ蛋白質(zhì)的小鼠,。結(jié)果證實(shí)，由于缺乏這兩種蛋白質(zhì),，這些實(shí)驗(yàn)小鼠體膚發(fā)育不良,，不能有效“鎖住”身體里的水分，小鼠在出生后不久就因嚴(yán)重脫水死亡,。
研究人員希望通過進(jìn)一步研究了解人體皮膚形成和修復(fù)機(jī)理,，揭開皮膚癌等上皮癌癥的致病原因。（生物谷Bioon.com）
生物谷推薦原始出處：
Nature Cell Biology 13 September 2009 | doi:10.1038/ncb1960
C/EBP and couple interfollicular keratinocyte proliferation arrest to commitment and terminal differentiation
Rodolphe G. Lopez1, Susana Garcia-Silva1, Susan J. Moore1, Oksana Bereshchenko1, Ana B. Martinez-Cruz2, Olga Ermakova1, Elke Kurz1, Jesus M. Paramio2 & Claus Nerlov1,3
Abstract
The transcriptional regulators that couple interfollicular basal keratinocyte proliferation arrest to commitment and differentiation are yet to be identified. Here we report that the basic region leucine zipper transcription factors C/EBP and C/EBP are co-expressed in basal keratinocytes, and are coordinately upregulated as keratinocytes exit the basal layer and undergo terminal differentiation. Mice lacking both C/EBP and in the epidermis showed increased proliferation of basal keratinocytes and impaired commitment to differentiation. This led to ectopic expression of keratin 14 (K14) and Np63 in suprabasal cells, decreased expression of spinous and granular layer proteins, parakeratosis and defective epidermal water barrier function. Knock-in mutagenesis revealed that C/EBP-E2F interaction was required for control of interfollicular epidermis (IFE) keratinocyte proliferation, but not for induction of spinous and granular layer markers, whereas C/EBP DNA binding was required for Np63 downregulation and K1/K10 induction. Finally, loss of C/EBP/ induced stem cell gene expression signatures in the epidermis. C/EBPs, therefore, couple basal keratinocyte cell cycle exit to commitment to differentiation through E2F repression and DNA binding, respectively, and may act to restrict the epidermal stem cell compartment.
1 EMBL Mouse Biology Unit, Monterotondo, 00016 Italy.
2 Molecular Oncology Unit, CIEMAT, Madrid, 28040 Spain.
3 Institute for Stem Cell Research and MRC Centre for Regenerative Medicine, University of Edinburgh, UK.
