存儲著我們的遺傳信息的DNA在我們的一生當中持續地遭受損傷。如果不能正確地修復，那麼DNA損傷會導致細胞死亡。而這又能夠導致組織衰竭和衰老或者誘導突變產生從而使得細胞不受控制地增殖而導致癌症。基因Brca1在調節DNA修復中發揮著作用。Brca1發生突變能夠導致人們患上家族性和散發性乳腺癌和卵巢癌。
在一項新的研究中，研究人員證實Brca1在維持毛囊幹細胞(follicle stem cell)中發揮著關鍵性的作用。相關研究於2012年12月27日在線發表在Genes and Development期刊上，論文標題為"BRCA1 deficiency in skin epidermis leads to selective loss of hair follicle stem cells and their progeny"。
研究人員證實一旦剔除表皮中與乳腺癌相關聯的基因Brca1，毛囊幹細胞呈現出高水平的DNA損傷和細胞死亡。這種細胞損傷和死亡誘導毛囊幹細胞過度增殖，並且最終讓它們耗竭，從而導致毛囊退化。相反，位於表皮中的形成皮膚屏障和皮脂腺(sebaceous gland)的其他類型幹細胞被維持，在基因BRCA1不存在時，它們也能夠繼續發揮正常的功能。這種差異體現出不同類型的成體幹細胞對BRCA1有不同的需求。論文第一作者Peggy Sotiropoulou評論道，"我們非常吃驚地觀察到位於相同組織的不同類型細胞對剔除相同的在DNA修復中發揮著至關重要作用的基因所作出的如此非常不同的反應。"
這項對於人們理解不同類型成體幹細胞中的DNA修復機制以及它們的不同激活階段是非常重要的。如果體內其他的幹細胞也需要BRCA1 才能存活的話，那麼這種研究結果可能潛在地解釋為何女性的Brac1突變偏好地只導致乳腺癌和卵巢癌產生。(生物谷Bioon.com)
BRCA1 deficiency in skin epidermis leads to selective loss of hair follicle stem cells and their progeny
Panagiota A. Sotiropoulou1,5,6, Andrea E. Karambelas1,5, Maud Debaugnies1, Aurelie Candi1, Peter Bouwman2, Virginie Moers1, Tatiana Revenco1, Ana Sofia Rocha1, Kiyotoshi Sekiguchi3, Jos Jonkers2 and Cedric Blanpain1,4,6
The accurate maintenance of genomic integrity is essential for tissue homeostasis. Deregulation of this process leads to cancer and aging. BRCA1 is a critical mediator of this process. Here, we performed conditional deletion of Brca1 during epidermal development and found that BRCA1 is specifically required for hair follicle (HF) formation and for development of adult HF stem cells (SCs). Mice deficient for Brca1 in the epidermis are hairless and display a reduced number of HFs that degenerate progressively. Surprisingly, the interfollicular epidermis and the sebaceous glands remain unaffected by Brca1 deletion. Interestingly, HF matrix transient amplifying progenitors present increased DNA damage, p53 stabilization, and caspase-dependent apoptosis compared with the interfollicular and sebaceous progenitors, leading to hyperproliferation, apoptosis, and subsequent depletion of the prospective adult HF SCs. Concomitant deletion of p53 and Brca1 rescues the defect of HF morphogenesis and loss of HF SCs. During adult homeostasis, BRCA1 is dispensable for quiescent bulge SCs, but upon their activation during HF regeneration, Brca1 deletion causes apoptosis and depletion of Brca1-deficient bulge SCs. Our data reveal a major difference in the requirement of BRCA1 between different types of epidermal SCs and progenitors and during the different activation stages of adult HF SCs.