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Identifying Mammary Epithelial Stem and Progenitor Cells

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Genetically Engineered Mice for Cancer Research

Abstract

The adult mouse mammary gland is composed of a branched ductal epithelium, which is embedded in a fatty stroma, termed the fat pad, comprising largely adipocytes but also fibroblasts, macrophages, and endothelial cells (Daniel and Silberstein 1987; Sakakura 1991). The various branches of the mammary tree are connected to a primary duct that terminates at the skin surface through the nipple. The mammary epithelium initially develops during embryogenesis from the ectoderm by cell migration and proliferation thus forming mammary buds, which subsequently sprout a rudimentary ductal tree that is present at birth (Sakakura 1987). Further mammary gland development is completed postnatally in defined stages (puberty, pregnancy, lactation, and involution), which are coupled to the sexual maturation and reproductive status of the animal (Fig. 12.1) (Hennighausen and Robinson 1998).

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References

  • Alexander CM, Puchalski J, Klos KS, Badders N, Ailles L, Kim CF, Dirks P, Smalley MJ (2009) Separating stem cells by flow cytometry: reducing variability for solid tissues. Cell Stem Cell 5:579–583

    Article  PubMed  CAS  Google Scholar 

  • Armstrong L, Stojkovic M, Dimmick I, Ahmad S, Stojkovic P, Hole N, Lako M (2004) Phenotypic characterization of murine primitive hematopoietic progenitor cells isolated on basis of aldehyde dehydrogenase activity. Stem Cells 22:1142–1151

    Article  PubMed  Google Scholar 

  • Asselin-Labat ML, Shackleton M, Stingl J, Vaillant F, Forrest NC, Eaves CJ, Visvader JE, Lindeman GJ (2006) Steroid hormone receptor status of mouse mammary stem cells. J Natl Cancer Inst 98:1011–1014

    Article  PubMed  CAS  Google Scholar 

  • Asselin-Labat ML, Sutherland KD, Barker H, Thomas R, Shackleton M, Forrest NC, Hartley L, Robb L, Grosveld FG, van der Wees J et al (2007) Gata-3 is an essential regulator of mammary-gland morphogenesis and luminal-cell differentiation. Nat Cell Biol 9:201–209

    Article  PubMed  CAS  Google Scholar 

  • Booth BW, Boulanger CA, Smith GH (2007) Alveolar progenitor cells develop in mouse mammary glands independent of pregnancy and lactation. J Cell Physiol 212:729–736

    Article  PubMed  CAS  Google Scholar 

  • Booth BW, Boulanger CA, Smith GH (2008) Stem cells and the mammary microenvironment. Breast Dis 29:57–67

    PubMed  Google Scholar 

  • Boulanger CA, Wagner KU, Smith GH (2005) Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGF-beta1 expression. Oncogene 24:552–560

    Article  PubMed  CAS  Google Scholar 

  • Bruno, R.D., and Smith, G.H. 2010. Functional Characterization of Stem Cell Activity in the Mouse Mammary Gland. Stem Cell Rev.

    Google Scholar 

  • Chepko G, Smith GH (1999) Mammary epithelial stem cells: our current understanding. J Mammary Gland Biol Neoplasia 4:35–52

    Article  PubMed  CAS  Google Scholar 

  • Cicalese A, Bonizzi G, Pasi CE, Faretta M, Ronzoni S, Giulini B, Brisken C, Minucci S, Di Fiore PP, Pelicci PG (2009) The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 138:1083–1095

    Article  PubMed  CAS  Google Scholar 

  • Corti S, Locatelli F, Papadimitriou D, Donadoni C, Salani S, Del Bo R, Strazzer S, Bresolin N, Comi GP (2006) Identification of a primitive brain-derived neural stem cell population based on aldehyde dehydrogenase activity. Stem Cells 24:975–985

    Article  PubMed  CAS  Google Scholar 

  • Daniel CW (1973) Finite growth span of mouse mammary gland serially propagated in vivo. Experientia 29:1422–1424

    Article  PubMed  CAS  Google Scholar 

  • Daniel CW, Shannon JM, Cunha GR (1983) Transplanted mammary epithelium grows in association with host stroma: aging of serially transplanted mammary gland is intrinsic to epithelial cells. Mech Ageing Dev 23:259–264

    Article  PubMed  CAS  Google Scholar 

  • Daniel CW, Silberstein GB (1987) Postnatal development of the rodent mammary gland. Plenum, New York

    Google Scholar 

  • DeOme KB, Faulkin LJ Jr, Bern HA, Blair PB (1959) Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res 19:515–520

    PubMed  CAS  Google Scholar 

  • Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ, Wicha MS (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17:1253–1270

    Article  PubMed  CAS  Google Scholar 

  • Eirew P, Stingl J, Raouf A, Turashvili G, Aparicio S, Emerman JT, Eaves CJ (2008) A method for quantifying normal human mammary epithelial stem cells with in vivo regenerative ability. Nat Med 14:1384–1389

    Article  PubMed  CAS  Google Scholar 

  • Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer CG, Liu S et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1:555–567

    Article  PubMed  CAS  Google Scholar 

  • Hennighausen L, Robinson GW (1998) Think globally, act locally: the making of a mouse mammary gland. Genes Dev 12:449–455

    Article  PubMed  CAS  Google Scholar 

  • Hulett HR, Bonner WA, Barrett J, Herzenberg LA (1969) Cell sorting: automated separation of mammalian cells as a function of intracellular fluorescence. Science 166:747–749

    Article  PubMed  CAS  Google Scholar 

  • Kordon EC, Smith GH (1998) An entire functional mammary gland may comprise the progeny from a single cell. Development 125:1921–1930

    PubMed  CAS  Google Scholar 

  • Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, Richardson A, Weinberg RA (2004) Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci USA 101:4966–4971

    Article  PubMed  CAS  Google Scholar 

  • Kurpios NA, MacNeil L, Shepherd TG, Gludish DW, Giacomelli AO, Hassell JA (2009) The Pea3 Ets transcription factor regulates differentiation of multipotent progenitor cells during mammary gland development. Dev Biol 325:106–121

    Article  PubMed  CAS  Google Scholar 

  • Lanzkron SM, Collector MI, Sharkis SJ (1999) Hematopoietic stem cell tracking in vivo: a comparison of short-term and long-term repopulating cells. Blood 93:1916–1921

    PubMed  CAS  Google Scholar 

  • Li W, Ferguson BJ, Khaled WT, Tevendale M, Stingl J, Poli V, Rich T, Salomoni P, Watson CJ (2009) PML depletion disrupts normal mammary gland development and skews the composition of the mammary luminal cell progenitor pool. Proc Natl Acad Sci USA 106:4725–4730

    Article  PubMed  CAS  Google Scholar 

  • Liao MJ, Zhang CC, Zhou B, Zimonjic DB, Mani SA, Kaba M, Gifford A, Reinhardt F, Popescu NC, Guo W et al (2007) Enrichment of a population of mammary gland cells that form mammospheres and have in vivo repopulating activity. Cancer Res 67:8131–8138

    Article  PubMed  CAS  Google Scholar 

  • Matulka LA, Triplett AA, Wagner KU (2007) Parity-induced mammary epithelial cells are multipotent and express cell surface markers associated with stem cells. Dev Biol 303:29–44

    Article  PubMed  CAS  Google Scholar 

  • Outzen HC, Custer RP (1975) Growth of human normal and neoplastic mammary tissues in the cleared mammary fat pad of the nude mouse. J Natl Cancer Inst 55:1461–1466

    PubMed  CAS  Google Scholar 

  • Pece S, Tosoni D, Confalonieri S, Mazzarol G, Vecchi M, Ronzoni S, Bernard L, Viale G, Pelicci PG, Di Fiore PP (2010) Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content. Cell 140:62–73

    Article  PubMed  CAS  Google Scholar 

  • Petersen OW, Polyak K (2010) Stem cells in the human breast. Cold Spring Harb Perspect Biol 2:a003160

    Article  PubMed  Google Scholar 

  • Proia DA, Kuperwasser C (2006) Reconstruction of human mammary tissues in a mouse model. Nat Protoc 1:206–214

    Article  PubMed  CAS  Google Scholar 

  • Sakakura T (1987) Mammary embryogenesis. Plenum Publishing Corporation, New York

    Google Scholar 

  • Sakakura T (1991) New aspects of stroma-parenchyma relations in mammary gland differentiation. Int Rev Cytol 125:165–202

    Article  PubMed  CAS  Google Scholar 

  • Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, Asselin-Labat ML, Wu L, Lindeman GJ, Visvader JE (2006) Generation of a functional mammary gland from a single stem cell. Nature 439:84–88

    Article  PubMed  CAS  Google Scholar 

  • Sheffield LG (1988) Organization and growth of mammary epithelia in the mammary gland fat pad. J Dairy Sci 71:2855–2874

    Article  PubMed  CAS  Google Scholar 

  • Sleeman KE, Kendrick H, Ashworth A, Isacke CM, Smalley MJ (2006) CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells. Breast Cancer Res 8:R7

    Article  PubMed  Google Scholar 

  • Sleeman KE, Kendrick H, Robertson D, Isacke CM, Ashworth A, Smalley MJ (2007) Dissociation of estrogen receptor expression and in vivo stem cell activity in the mammary gland. J Cell Biol 176:19–26

    Article  PubMed  CAS  Google Scholar 

  • Smalley MJ, Titley J, O’Hare MJ (1998) Clonal characterization of mouse mammary luminal epithelial and myoepithelial cells separated by fluorescence-activated cell sorting. In Vitro Cell Dev Biol Anim 34:711–721

    Article  PubMed  CAS  Google Scholar 

  • Smith GH (1996) Experimental mammary epithelial morphogenesis in an in vivo model: evidence for distinct cellular progenitors of the ductal and lobular phenotype. Breast Cancer Res Treat 39:21–31

    Article  PubMed  CAS  Google Scholar 

  • Smith GH, Boulanger CA (2002) Mammary stem cell repertoire: new insights in aging epithelial populations. Mech Ageing Dev 123:1505–1519

    Article  PubMed  CAS  Google Scholar 

  • Smith GH, Boulanger CA (2003) Mammary epithelial stem cells: transplantation and self-renewal analysis. Cell Prolif 36(Suppl 1):3–15

    Article  PubMed  CAS  Google Scholar 

  • Smith GH, Chepko G (2001) Mammary epithelial stem cells. Microsc Res Tech 52:190–203

    Article  PubMed  CAS  Google Scholar 

  • Smith GH, Medina D (1988) A morphologically distinct candidate for an epithelial stem cell in mouse mammary gland. J Cell Sci 90(Pt 1):173–183

    PubMed  Google Scholar 

  • Stingl J, Eaves CJ, Zandieh I, Emerman JT (2001) Characterization of bipotent mammary epithelial progenitor cells in normal adult human breast tissue. Breast Cancer Res Treat 67:93–109

    Article  PubMed  CAS  Google Scholar 

  • Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, Choi D, Li HI, Eaves CJ (2006) Purification and unique properties of mammary epithelial stem cells. Nature 439:993–997

    PubMed  CAS  Google Scholar 

  • Visvader JE (2009) Keeping abreast of the mammary epithelial hierarchy and breast tumorigenesis. Genes Dev 23:2563–2577

    Article  PubMed  CAS  Google Scholar 

  • Wagner KU, Boulanger CA, Henry MD, Sgagias M, Hennighausen L, Smith GH (2002) An adjunct mammary epithelial cell population in parous females: its role in functional adaptation and tissue renewal. Development 129:1377–1386

    PubMed  CAS  Google Scholar 

  • Welm BE, Tepera SB, Venezia T, Graubert TA, Rosen JM, Goodell MA (2002) Sca-1(pos) cells in the mouse mammary gland represent an enriched progenitor cell population. Dev Biol 245:42–56

    Article  PubMed  CAS  Google Scholar 

  • Williams JM, Daniel CW (1983) Mammary ductal elongation: differentiation of myoepithelium and basal lamina during branching morphogenesis. Dev Biol 97:274–290

    Article  PubMed  CAS  Google Scholar 

  • Youn BS, Sen A, Kallos MS, Behie LA, Girgis-Gabardo A, Kurpios N, Barcelon M, Hassell JA (2005) Large-scale expansion of mammary epithelial stem cell aggregates in suspension bioreactors. Biotechnol Prog 21:984–993

    Article  PubMed  CAS  Google Scholar 

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Correspondence to John A. Hassell .

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Giacomelli, A.O., Hallett, R.M., Hassell, J.A. (2012). Identifying Mammary Epithelial Stem and Progenitor Cells. In: Green, J., Ried, T. (eds) Genetically Engineered Mice for Cancer Research. Springer, New York, NY. https://doi.org/10.1007/978-0-387-69805-2_12

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