β1 integrin deletion from the basal compartment of the mammary epithelium affects stem cells
β1 integrin deletion from the basal compartment of the mammary epithelium affects stem cells
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DOI：
10.1038/ncb1734
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发表时间：
2008-06-01
影响因子：
21.3
通讯作者：
Glukhova, Marina A.
中科院分区：
文献类型：
--
作者：
Taddei, Ilaria;Deugnier, Marie-Ange;Glukhova, Marina A.
乳腺上皮包含两种主要细胞类型：基底细胞和管腔细胞。基底细胞直接与细胞外基质 (ECM) 相互作用，并比管腔细胞表达更高水平的 ECM 受体、整合素。我们发现，从基底细胞中删除β1整合素会消除乳腺上皮的再生潜力并影响乳腺发育。突变上皮的特征是妊娠期异常的导管分支模式和异常的形态发生，尽管在妊娠末期，分泌性肺泡由β1整合素阳性祖细胞发育而来。 β 1 整合素的缺乏改变了基底细胞分裂轴的方向，在突变上皮中，与对照组织相反，在腔室中发现了通过遗传标记鉴定的β 1 整合素缺失基底细胞的后代。这些结果首次揭示了β1整合素介导的基底乳腺上皮细胞-ECM相互作用在维持功能性干细胞群、乳腺形态发生和两种主要乳腺细胞谱系分离中的重要作用。
The mammary gland epithelium comprises two major cell types: basal and luminal. Basal cells interact directly with the extracellular matrix (ECM) and express higher levels of the ECM receptors, integrins, than luminal cells. We show that deletion of beta 1 integrin from basal cells abolishes the regenerative potential of the mammary epithelium and affects mammary gland development. The mutant epithelium was characterized by an abnormal ductal branching pattern and aberrant morphogenesis in pregnancy, although at the end of gestation, the secretory alveoli developed from beta 1 integrin-positive progenitors. Lack of beta 1 integrin altered the orientation of the basal-cell division axis and in mutant epithelium, in contrast to control tissue, the progeny of beta 1 integrin-null basal cells, identified by a genetic marker, was found in the luminal compartment. These results reveal, for the first time, the essential role of the basal mammary epithelial cell-ECM interactions mediated by beta 1 integrins in the maintenance of a functional stem cell population, mammary morphogenesis and segregation of the two major mammary cell lineages.