Luminal progenitors restrict their lineage potential during mammary gland development.
Luminal progenitors restrict their lineage potential during mammary gland development.
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DOI：
10.1371/journal.pbio.1002069
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发表时间：
2015-02
期刊：
影响因子：
9.8
通讯作者：
Fre S
中科院分区：
文献类型：
--
作者：
Rodilla V;Dasti A;Huyghe M;Lafkas D;Laurent C;Reyal F;Fre S
指导乳腺形态发生的干细胞和祖细胞之间的等级关系仍然不清楚。虽然已经在肌上皮间室中发现了多潜能的基础干细胞，但腔前体细胞在体内的谱系潜力尚不清楚。在这里，我们使用之前与乳腺发育和肿瘤发生有关的Notch1受体的表达，通过谱系追踪来阐明乳腺干/祖细胞的分级组织。我们发现Notch1的表达识别了胚胎乳房芽中的多潜能干细胞，在乳腺导管形态发生期间，这些干细胞逐渐限制了它们的谱系潜力，从而在出生后唯一地产生了ERα阴性的腔系。重要的是，我们的结果表明，Notch1标记的细胞代表着在怀孕期间扩张的肺泡祖细胞，并在多次连续内陷中存活下来。这项研究揭示了出生后的腔上皮细胞来自不同的自我维持的谱系，这可能代表了不同乳腺癌亚型的起源细胞。胚胎乳腺中表达Notch1受体的干细胞最初具有多能性和高度再生能力，但它们逐渐将其谱系潜力限制在乳腺导管的管腔内，在那里它们可能导致乳腺癌。组织特异性干细胞被认为是多能的，因此能够产生其来源组织的所有细胞类型。然而，在乳腺上皮中，多能和单能成体干细胞的存在目前还在争论中。在这项研究中，我们鉴定并鉴定了一组表达Notch1受体的乳腺腔祖细胞。通过谱系追踪实验，我们发现这些细胞是自我维持的单一能力的成体祖细胞，具有很高的自我更新能力。尽管这些细胞缺乏雌激素和孕激素受体，但它们对激素高度敏感。重要的是，Notch1表达的细胞在胚胎乳房发育过程中是多能的，当它们可以产生所有类型的乳房细胞时，它们在出生后成为血统受限的。这项研究中描述的细胞也表现出广泛的可塑性，因为它们可以在移植实验中重新填充整个乳腺。我们的研究表明，Notch1受体是识别缺乏激素受体表达的腔前体细胞的特异性标记物，这可能是乳腺癌发生的关键。
The hierarchical relationships between stem cells and progenitors that guide mammary gland morphogenesis are still poorly defined. While multipotent basal stem cells have been found within the myoepithelial compartment, the in vivo lineage potential of luminal progenitors is unclear. Here we used the expression of the Notch1 receptor, previously implicated in mammary gland development and tumorigenesis, to elucidate the hierarchical organization of mammary stem/progenitor cells by lineage tracing. We found that Notch1 expression identifies multipotent stem cells in the embryonic mammary bud, which progressively restrict their lineage potential during mammary ductal morphogenesis to exclusively generate an ERαneg luminal lineage postnatally. Importantly, our results show that Notch1-labelled cells represent the alveolar progenitors that expand during pregnancy and survive multiple successive involutions. This study reveals that postnatal luminal epithelial cells derive from distinct self-sustained lineages that may represent the cells of origin of different breast cancer subtypes. Stem cells in the embryonic mammary gland that express the Notch1 receptor are initially multipotent and highly regenerative, but they progressively restrict their lineage potential to the lumen of the mammary duct, where they may give rise to breast cancer. Tissue-specific stem cells are believed to be multipotent, thus able to generate all cell types of their tissue of origin. In the mammary gland epithelium, however, the existence of multipotent versus unipotent adult stem cells is currently under debate. In this study, we have identified and characterized a population of mammary luminal progenitors that express the Notch1 receptor. Using lineage tracing experiments, we found that these cells are self-sustained unipotent adult progenitors with high self-renewal capacity. Although they lack estrogen and progesterone hormone receptors, these cells are highly responsive to hormones. Importantly, Notch1-expressing cells are multipotent during embryonic mammary development, when they can give rise to all mammary cell types, while they become lineage-restricted postnatally. The cells characterized in this study also present extensive plasticity, as they can repopulate the entire mammary gland in transplantation experiments. Our study reveals that the Notch1 receptor is a specific marker for the identification of luminal progenitors that lack expression of hormone receptors and that can be critical for breast cancer initiation.
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影响因子：
23.9
作者：
Bouras, Toula;Pal, Bhupinder;Visvader, Jane E.
通讯作者：
Visvader, Jane E.
影响因子：
14.8
作者：
Eirew, Peter;Stingl, John;Eaves, Connie J.
通讯作者：
Eaves, Connie J.
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
DOI：
10.1186/bcr3593
发表时间：
2014-01-07
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Chang TH;Kunasegaran K;Tarulli GA;De Silva D;Voorhoeve PM;Pietersen AM
通讯作者：
Pietersen AM
影响因子：
21.3
作者：
Asselin-Labat, Marie-Liesse;Sutherland, Kate D.;Visvader, Jane E.
通讯作者：
Visvader, Jane E.