Notch3 marks clonogenic mammary luminal progenitor cells in vivo.
Notch3 marks clonogenic mammary luminal progenitor cells in vivo.
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DOI：
10.1083/jcb.201307046
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发表时间：
2013-10-14
期刊：
影响因子：
--
通讯作者：
Fre S
中科院分区：
文献类型：
--
作者：
Lafkas D;Rodilla V;Huyghe M;Mourao L;Kiaris H;Fre S
NOTCH3的表达是乳腺中高度克隆性和暂时静止的管腔祖细胞群体的特征，其扩张受到Notch3受体活性的限制。乳腺干细胞和祖细胞的特性仍然知之甚少，主要是由于缺乏强有力的标记。Notch信号通路与乳腺发育以及乳腺组织中肿瘤的发生有关。Notch3受体的高表达与高度侵袭性的“三阴性”人类乳腺癌有关。然而，在乳腺中表达这种Notch类似物的特定细胞仍然未知。使用条件诱导的Notch3-CreERT2SAT转基因小鼠，我们在整个乳腺发育过程中对表达Notch3的细胞进行了遗传标记，并在体内跟踪了它们的谱系。我们证明了Notch3在一个高度克隆性和短暂静止的管状血统形成的管状祖细胞群体中表达。这些细胞能够在多次连续怀孕中存活下来，这表明它们具有自我更新的能力。我们的结果还揭示了Notch3受体在限制这些细胞的增殖和随后的克隆性扩张中的作用。
Notch3 expression characterizes a highly clonogenic and transiently quiescent luminal progenitor population in the mammary gland, the expansion of which is restricted by Notch3 receptor activity. The identity of mammary stem and progenitor cells remains poorly understood, mainly as a result of the lack of robust markers. The Notch signaling pathway has been implicated in mammary gland development as well as in tumorigenesis in this tissue. Elevated expression of the Notch3 receptor has been correlated to the highly aggressive “triple negative” human breast cancer. However, the specific cells expressing this Notch paralogue in the mammary gland remain unknown. Using a conditionally inducible Notch3-CreERT2SAT transgenic mouse, we genetically marked Notch3-expressing cells throughout mammary gland development and followed their lineage in vivo. We demonstrate that Notch3 is expressed in a highly clonogenic and transiently quiescent luminal progenitor population that gives rise to a ductal lineage. These cells are capable of surviving multiple successive pregnancies, suggesting a capacity to self-renew. Our results also uncover a role for the Notch3 receptor in restricting the proliferation and consequent clonal expansion of these cells.
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影响因子：
8
作者：
Turner, N.;Lambros, M. B.;Horlings, H. M.;Pearson, A.;Sharpe, R.;Natrajan, R.;Geyer, F. C.;van Kouwenhove, M.;Kreike, B.;Mackay, A.;Ashworth, A.;de Vijver, M. J. van;Reis-Filho, J. S.
通讯作者：
Reis-Filho, J. S.
影响因子：
23.9
作者：
Bouras, Toula;Pal, Bhupinder;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
DOI：
10.1186/bcr1411
发表时间：
2006
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Oakes SR;Hilton HN;Ormandy CJ
通讯作者：
Ormandy CJ
Notch谱系和肠道干细胞的活性由一组新的敲入小鼠确定。
影响因子：
3.7
作者：
Fre S;Hannezo E;Sale S;Huyghe M;Lafkas D;Kissel H;Louvi A;Greve J;Louvard D;Artavanis-Tsakonas S
通讯作者：
Artavanis-Tsakonas S
影响因子：
4.6
作者：
Alunni, Alessandro;Krecsmarik, Monika;Bally-Cuif, Laure
通讯作者：
Bally-Cuif, Laure