欧洲研究人员13日在英国《自然－细胞生物学》杂志网络版上发表报告说，他们发现两种蛋白质能控制皮肤干细胞转化成皮肤细胞。这一发现将有助于研究人员更好地了解皮肤生成机理及皮肤癌的致病原因等。
欧洲分子生物实验室的研究人员通过动物实验发现，蛋白质C／EBPα和C／EBPβ在控制皮肤干细胞何时停止增殖、何时开始分化成皮肤细胞的过程中发挥着重要作用。
研究人员随后利用基因工程技术培育出身体不携带C／EBPα和C／EBPβ蛋白质的小鼠。结果证实，由于缺乏这两种蛋白质，这些实验小鼠体肤发育不良，不能有效“锁住”身体里的水分，小鼠在出生后不久就因严重脱水死亡。
研究人员希望通过进一步研究了解人体皮肤形成和修复机理，揭开皮肤癌等上皮癌症的致病原因。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
