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β1 Integrin deletion from the basal compartment of the mammary epithelium affects stem cells


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 β1 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 β1 integrin-positive progenitors. Lack of β1 integrin altered the orientation of the basal-cell division axis and in mutant epithelium, in contrast to control tissue, the progeny of β1 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 β1 integrins in the maintenance of a functional stem cell population, mammary morphogenesis and segregation of the two major mammary cell lineages.

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Figure 1: Abnormal ductal morphogenesis in the mammary epithelium presenting conditional deletion of the β1 integrin gene in basal epithelial cells.
Figure 2: Lack of functional stem cells in K5Cre;itgb1F/F epithelium.
Figure 3: Perturbation of lobuloalveolar development in K5Cre;itgb1F/F mammary epithelium.
Figure 4: Altered orientation of the basal-cell division axis in K5Cre;itgb1F/F mammary epithelium.
Figure 5: K5-negative progenitors give rise to functional alveoli late in pregnancy.

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We are particularly grateful to I. Grandjean, and the personnel of the animal facilities at Institut Curie for taking care of the mice, and to Z. Maciorowski and A. Viguier for assistance with FACS analyses. We would also like to thank J. L. Jorcano for providing the K5-cre mice, M. Bissell, C. Brakebusch and M. Moumen for valuable discussions, A.-M. Valles for comments on the manuscript and M. Denoyelle for technical assistance. This work was supported by the Association pour la Recherche contre le Cancer (ARC 3295 and 3771) and La Ligue Nationale Contre le Cancer (Equipe Labelisée 2006). I.T. was supported by a grant from Fondation pour la Recherche Médicale (FRM). M.M.F. and M.A.D. are Chargés de Recherche, and M.A.G. is Directeur de Recherche at the Institut National de la Santé et de la Recherche Médicale (INSERM).

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Correspondence to Marina A. Glukhova.

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Supplementary Figures S1, S2, S3, S4, S5, Supplementary Table S1 and Supplementary Data (PDF 992 kb)

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Taddei, I., Deugnier, MA., Faraldo, M. et al. β1 Integrin deletion from the basal compartment of the mammary epithelium affects stem cells. Nat Cell Biol 10, 716–722 (2008).

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