最近科学家们发现了老鼠乳腺干细胞（MaSC）及其祖细胞群落，而这些发现大大促进了对于干细胞世系分化基因控制的研究。在2008年10月9日出版的《细胞—干细胞》（Cell Stem Cell）上，来自澳大利亚的Bouras等科学家发表文章称，他们发现了Notch信号途径在调控乳房干细胞功能和乳房上皮层级当中所发挥的作用。

      Notch是一种跨膜的受体，它们广泛存在于各种动物细胞中。Notch信号途径对于多种组织和细胞命运非常重要，包括表皮、神经、血液和肌肉等。在本期的封面文章中，研究人员发现，敲除MaSC富集细胞群当中的规范Notch效应子Cbf-1，将导致干细胞活性的增强，并产生异常的结构。以上发现表明，内生的Notch信号对于限制MaSC扩展起到了一定作用。

      同时科学家们还发现，在导管上皮（ductal luminal epithelium）中，Notch被预先激活，这表明Notch信号能特异性针对luminal祖细胞，luminal组细胞的扩展将导致增生肥大以及肿瘤的发生。因此在文章最后，作者认为他们的发现揭示了Notch信号在MaSC和luminal细胞决定方面所起到的作用，并且研究结果还进一步表明不当的Notch激活将促进luminal祖细胞的自我更新和转化。

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.