（封面圖片：老鼠乳腺干細(xì)胞產(chǎn)生的乳腺組織的整體圖像。這些乳腺干細(xì)胞被逆轉(zhuǎn)錄病毒處理過,，逆轉(zhuǎn)錄病毒表達(dá)對抗Notch效應(yīng)子Cbf-1的shRNA,。轉(zhuǎn)化后的干細(xì)胞移植到小鼠的乳腺脂肪墊中,，并且在8周的培養(yǎng)后取出。結(jié)果發(fā)現(xiàn)Notch信號對限制乳腺發(fā)育過程中MaSC的擴展起到了重要作用,。）
最近科學(xué)家們發(fā)現(xiàn)了老鼠乳腺干細(xì)胞（MaSC）及其祖細(xì)胞群落,，而這些發(fā)現(xiàn)大大促進了對于干細(xì)胞世系分化基因控制的研究。在2008年10月9日出版的《細(xì)胞—干細(xì)胞》（Cell Stem Cell）上,，來自澳大利亞的Bouras等科學(xué)家發(fā)表文章稱,，他們發(fā)現(xiàn)了Notch信號途徑在調(diào)控乳房干細(xì)胞功能和乳房上皮層級當(dāng)中所發(fā)揮的作用。
Notch是一種跨膜的受體,，它們廣泛存在于各種動物細(xì)胞中,。Notch信號途徑對于多種組織和細(xì)胞命運非常重要，包括表皮,、神經(jīng),、血液和肌肉等。在本期的封面文章中,，研究人員發(fā)現(xiàn),，敲除MaSC富集細(xì)胞群當(dāng)中的規(guī)范Notch效應(yīng)子Cbf-1，將導(dǎo)致干細(xì)胞活性的增強,，并產(chǎn)生異常的結(jié)構(gòu),。以上發(fā)現(xiàn)表明，內(nèi)生的Notch信號對于限制MaSC擴展起到了一定作用,。
同時科學(xué)家們還發(fā)現(xiàn),，在導(dǎo)管上皮（ductal luminal epithelium）中，Notch被預(yù)先激活，這表明Notch信號能特異性針對luminal祖細(xì)胞,，luminal組細(xì)胞的擴展將導(dǎo)致增生肥大以及腫瘤的發(fā)生,。因此在文章最后，作者認(rèn)為他們的發(fā)現(xiàn)揭示了Notch信號在MaSC和luminal細(xì)胞決定方面所起到的作用,，并且研究結(jié)果還進一步表明不當(dāng)?shù)腘otch激活將促進luminal祖細(xì)胞的自我更新和轉(zhuǎn)化,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell Stem Cell，Vol 3, 429-441, 09 October 2008,，Toula Bouras, Jane E. Visvader
Notch Signaling Regulates Mammary Stem Cell Function and Luminal Cell-Fate Commitment
Toula Bouras,1,3 Bhupinder Pal,1,3 Fran?ois Vaillant,1 Gwyndolen Harburg,1 Marie-Liesse Asselin-Labat,1 Samantha R. Oakes,1 Geoffrey J. Lindeman,1,2 and Jane E. Visvader1,
1 VBCRC Laboratory, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
2 Department of Medical Oncology, Royal Melbourne Hospital, Parkville, Victoria 3050, Australia
Summary
The recent identification of mouse mammary stem cells (MaSCs) and progenitor subpopulations has enhanced the prospect of investigating the genetic control of their lineage specification and differentiation. Here we have explored the role of the Notch pathway within the mammary epithelial hierarchy. We show that knockdown of the canonical Notch effector Cbf-1 in the MaSC-enriched population results in increased stem cell activity in vivo as well as the formation of aberrant end buds, implying a role for endogenous Notch signaling in restricting MaSC expansion. Conversely, Notch was found to be preferentially activated in the ductal luminal epithelium in vivo and promoted commitment of MaSCs exclusively along the luminal lineage. Notably, constitutive Notch signaling specifically targeted luminal progenitor cells for expansion, leading to hyperplasia and tumorigenesis. These findings reveal key roles for Notch signaling in MaSCs and luminal cell commitment and further suggest that inappropriate Notch activation promotes the self-renewal and transformation of luminal progenitor cells.
