New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells.
New insights into lineage restriction of mammary gland epithelium using parity-identified mammary epithelial cells.
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DOI：
10.1186/bcr3593
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发表时间：
2014-01-07
期刊：
影响因子：
--
通讯作者：
Pietersen AM
中科院分区：
文献类型：
--
作者：
Chang TH;Kunasegaran K;Tarulli GA;De Silva D;Voorhoeve PM;Pietersen AM
经产次鉴定的乳腺上皮细胞（PI-MEC）是一个有趣的细胞亚群，因为它们在退化中存活，并且是乳腺肿瘤中人表皮生长因子受体2（HER 2）/neu转化的假定靶点。根据测定的类型，PI-MEC被指定为小叶限制性祖细胞或多能干/祖细胞。据报道，PI-MEC是基于流式细胞术的乳腺上皮基础群体的一部分。我们研究了完整乳腺中PI-MEC的细胞特性和谱系潜力。我们进行了定量和定性分析的贡献PI-MEC乳腺上皮细胞谱系在怀孕和退化的乳腺免疫组织化学，荧光激活细胞分选（FACS），定量聚合酶链反应。PI-MEC在妊娠期间通过激活乳清酸性蛋白（WAP）-Cre进行标记，导致黄色荧光蛋白的永久表达。退化后，PI-MEC仅存在于乳腺导管的管腔层中。在妊娠期间，PI-MEC对肺泡小叶的腔层而不是基底层有贡献。引人注目的是，尽管肺泡中的所有腔雌激素受体（ER）阴性细胞都可以来自PI-MEC，但肺泡ER阳性细胞是未标记的，并且使人联想到Notch 2示踪的L细胞。值得注意的是，我们观察到一个显着的人口未标记的肺泡祖细胞类似PI-MEC的基础上转录和组织学分析。我们证明PI-MEC是管腔细胞强调了不仅基底细胞在移植测定中显示多谱系潜力。然而，PI-MEC在未受干扰的乳腺中的谱系潜力明显限于分泌腺泡谱系的管腔ER阴性细胞。一个未标记的，但功能相似的人口管腔肺泡祖细胞的鉴定提出了一个问题，是否PI-MEC是一个独特的人口或随机标记的结果。有趣的是，即使当肺泡的所有管腔ER阴性细胞都是PI-MEC衍生的时，基底细胞和细胞敏感细胞也来自不同的来源，这表明来自不同谱系的细胞的合作生长在肺泡发生中是常见的。
Parity-identified mammary epithelial cells (PI-MECs) are an interesting cellular subset because they survive involution and are a presumptive target for transformation by human epidermal growth factor receptor 2 (HER2)/neu in mammary tumors. Depending on the type of assay, PI-MECs have been designated lobule-restricted progenitors or multipotent stem/progenitor cells. PI-MECs were reported to be part of the basal population of mammary epithelium based on flow cytometry. We investigated the cellular identity and lineage potential of PI-MECs in intact mammary glands. We performed a quantitative and qualitative analysis of the contribution of PI-MECs to mammary epithelial cell lineages in pregnant and involuted mammary glands by immunohistochemistry, fluorescence-activated cells sorting (FACS), and quantitative polymerase chain reaction. PI-MECs were labeled by the activation of Whey Acidic Protein (WAP)-Cre during pregnancy that results in permanent expression of yellow fluorescent protein. After involution, PI-MECs are present exclusively in the luminal layer of mammary ducts. During pregnancy, PI-MECs contribute to the luminal layer but not the basal layer of alveolar lobules. Strikingly, whereas all luminal estrogen receptor (ER)-negative cells in an alveolus can be derived from PI-MECs, the alveolar ER-positive cells are unlabeled and reminiscent of Notch2-traced L cells. Notably, we observed a significant population of unlabeled alveolar progenitors that resemble PI-MECs based on transcriptional and histological analysis. Our demonstration that PI-MECs are luminal cells underscores that not only basal cells display multi-lineage potential in transplantation assays. However, the lineage potential of PI-MECs in unperturbed mammary glands is remarkably restricted to luminal ER-negative cells of the secretory alveolar lineage. The identification of an unlabeled but functionally similar population of luminal alveolar progenitor cells raises the question of whether PI-MECs are a unique population or the result of stochastic labeling. Interestingly, even when all luminal ER-negative cells of an alveolus are PI-MEC-derived, the basal cells and hormone-sensing cells are derived from a different source, indicating that cooperative outgrowth of cells from different lineages is common in alveologenesis.
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