Epithelial progenitors in the normal human mammary gland
Epithelial progenitors in the normal human mammary gland
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DOI：
10.1007/s10911-005-2540-7
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发表时间：
2005-01-01
影响因子：
2.5
通讯作者：
Eaves, CJ
中科院分区：
文献类型：
--
作者：
Stingl, J;Raouf, A;Eaves, CJ
人类乳腺在发育上组织为祖细胞的等级，其增殖能力和谱系选择逐渐受到限制。目前已鉴定出三种类型的人乳腺上皮细胞祖细胞。第一种被认为是管腔限制性祖细胞;在体外，在支持管腔和肌上皮细胞分化的条件下，该细胞产生分化的子细胞的克隆，所述子细胞对体内产生的管腔细胞的特征性标志物是唯一阳性的（即，角蛋白8/18和19，上皮细胞粘附分子[EpCAM]和MUC 1）。第二种类型是双能祖细胞。它通过其在单细胞测定中产生“混合”集落的能力来鉴定。这些集落含有表达管腔标记物的细胞的中心核心，其被具有形态和标记物（例如，角蛋白14（+））肌上皮细胞特征。体外连续传代富集的双能祖细胞群促进了第三类祖细胞的扩增，第三类祖细胞被认为是肌上皮限制性的，因为它只产生具有肌上皮特征的细胞。从新鲜分离的正常人乳腺细胞悬液中，可以前瞻性地分离出发光限制性和双能祖细胞作为不同的亚群。两者通过表达EpCAM和CD 49 f（α 6整联蛋白）而与乳腺组织中的许多其他细胞类型区分开。它们通过MUC 1的差异表达而彼此区分，MUC 1在管腔祖细胞上以高得多的水平表达。与这些祖细胞的作用，在体内产生的乳腺树的三维tubuloalveolar结构的产生，我们提出了一个模型，其中的承诺，管腔与肌上皮谱系可能发挥决定性的作用，在产生的肺泡和导管。
The human mammary gland is organized developmentally as a hierarchy of progenitor cells that become progressively restricted in their proliferative abilities and lineage options. Three types of human mammary epithelial cell progenitors are now identified. The first is thought to be a luminal-restricted progenitor; in vitro under conditions that support both luminal and myoepithelial cell differentiation, this cell produces clones of differentiating daughter cells that are exclusively positive for markers characteristic of luminal cells produced in vivo (i.e., keratins 8/18 and 19, epithelial cell adhesion molecule [EpCAM] and MUC1). The second type is a bipotent progenitor. It is identified by its ability to produce "mixed" colonies in single cell assays. These colonies contain a central core of cells expressing luminal markers surrounded by cells with a morphology and markers (e.g., keratin 14(+)) characteristic of myoepithelial cells. Serial passage in vitro of an enriched population of bipotent progenitors promotes the expansion of a third type of progenitor that is thought to be myoepithelial-restricted because it only produces cells with myoepithelial features. Luminal-restricted and bipotent progenitors can prospectively be isolated as distinct subpopulations from freshly dissociated suspensions of normal human mammary cells. Both are distinguished from many other cell types in mammary tissue by their expression of EpCAM and CD49f (alpha 6 integrin). They are distinguished from each other by their differential expression of MUC1, which is expressed at much higher levels on the luminal progenitors. To relate the role of these progenitors to the generation of the three-dimensional tubuloalveolar structure of the mammary tree produced in vivo, we propose a model in which the commitment to the luminal versus the myoepithelial lineage may play a determining role in the generation of alveoli and ducts.