title: s-SHIP promoter expression marks activated stem cells in developing mouse mammary tissue.
abstract: Mammary stem cells (MaSCs) play critical roles in normal development and perhaps tumorigenesis of the mammary gland. Using combined cell markers, adult MaSCs have been enriched in a basal cell population, but the exact identity of MaSCs remains unknown. We used the s-SHIP promoter to tag presumptive stem cells with GFP in the embryos of a transgenic mouse model. Here we show, in postnatal mammary gland development, that GFP(+) cap cells in puberty and basal alveolar bud cells in pregnancy each exhibit self-renewal and regenerative capabilities for all mammary epithelial cells of a new functional mammary gland upon transplantation. Single GFP(+) cells can regenerate the mammary epithelial network. GFP(+) mammary epithelial cells are p63(+), CD24(mod), CD49f(high), and CD29(high); are actively proliferating; and express s-SHIP mRNA. Overall, our results identify the activated MaSC population in vivo at the forefront of rapidly developing terminal end buds (puberty) and alveolar buds (pregnancy) in the mammary gland. In addition, GFP(+) basal cells are expanded in MMTV-Wnt1 breast tumors but not in ErbB2 tumors. These results enable MaSC in situ identification and isolation via a consistent single parameter using a new mouse model with applications for further analyses of normal and potential cancer stem cells.
authors.affiliation: Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Lixia
authors.initials: L
authors.lastname: Bai
authors.forename: Larry R
authors.initials: LR
authors.lastname: Rohrschneider
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000503:physiopathology; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D000072181:Inositol Polyphosphate 5-Phosphatases; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D049452:Green Fluorescent Proteins; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases
references.citation: Nature. 2008 Dec 4;456(7222):593-8
references.pmid: 19052619
references.citation: Blood. 2001 Oct 1;98(7):2028-38
references.pmid: 11567986
references.citation: Cell. 2008 Dec 12;135(6):1118-29
references.pmid: 19062086
references.citation: Nat Rev Cancer. 2007 Oct;7(10):791-9
references.pmid: 17851544
references.citation: Proc Natl Acad Sci U S A. 2007 Jan 2;104(1):181-6
references.pmid: 17185413
references.citation: Proc Natl Acad Sci U S A. 1968 Sep;61(1):53-60
references.pmid: 4301594
references.citation: Nature. 2007 Oct 25;449(7165):1003-7
references.pmid: 17934449
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4158-63
references.pmid: 15020770
references.citation: Nature. 2006 Jan 5;439(7072):84-8
references.pmid: 16397499
references.citation: J Cell Biol. 2007 Jan 1;176(1):19-26
references.pmid: 17190790
references.citation: Cell Stem Cell. 2009 Dec 4;5(6):579-83
references.pmid: 19951686
references.citation: Nat Rev Mol Cell Biol. 2005 Sep;6(9):715-25
references.pmid: 16231422
references.citation: Breast Cancer Res. 2008;10(3):402; author reply 403
references.pmid: 18522763
references.citation: Nat Genet. 2008 Nov;40(11):1291-9
references.pmid: 18849992
references.citation: Nature. 1999 Apr 22;398(6729):708-13
references.pmid: 10227293
references.citation: Methods. 2003 Jul;30(3):256-68
references.pmid: 12798140
references.citation: Dev Biol. 2005 Jul 15;283(2):503-21
references.pmid: 15978570
references.citation: Science. 2002 May 10;296(5570):1046-9
references.pmid: 12004111
references.citation: Nature. 2006 Feb 23;439(7079):993-7
references.pmid: 16395311
references.citation: Nature. 2009 Jan 29;457(7229):603-7
references.pmid: 19092805
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 30;105(39):14891-6
references.pmid: 18809919
references.citation: Nature. 2004 Nov 18;432(7015):396-401
references.pmid: 15549107
references.citation: J Natl Cancer Inst. 2006 Jul 19;98(14):1011-4
references.pmid: 16849684
references.citation: Breast Cancer Res. 2006;8(1):R7
references.pmid: 16417656
references.citation: Cell. 2007 May 4;129(3):523-36
references.pmid: 17482546
references.citation: Cell. 2007 Feb 9;128(3):445-58
references.pmid: 17289566
references.citation: Nat Rev Cancer. 2003 Nov;3(11):832-44
references.pmid: 14668814
references.citation: Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3871-6
references.pmid: 17360445
references.citation: J Exp Med. 1996 Apr 1;183(4):1797-806
references.pmid: 8666936
references.citation: Dev Biol. 2006 May 15;293(2):414-25
references.pmid: 16545360
references.citation: Cancer Cell. 2005 Jan;7(1):17-23
references.pmid: 15652746
references.citation: Development. 1998 May;125(10):1921-30
references.pmid: 9550724
references.citation: Cancer Res. 2008 Oct 1;68(19):7711-7
references.pmid: 18829523
references.citation: Nature. 1999 Apr 22;398(6729):714-8
references.pmid: 10227294
references.citation: Dev Biol. 2002 May 1;245(1):42-56
references.pmid: 11969254
references.citation: Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1680-5
references.pmid: 18230721
references.citation: Trends Mol Med. 2006 Nov;12(11):537-44
references.pmid: 17011236
references.citation: Dev Biol. 1983 Jun;97(2):274-90
references.pmid: 6852366
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15853-8
references.pmid: 14668450
references.citation: Genes Dev. 1991 Sep;5(9):1513-23
references.pmid: 1653172
references.citation: Cancer Res. 1959 Jun;19(5):515-20
references.pmid: 13663040
references.citation: Cell. 1995 Jan 13;80(1):83-93
references.pmid: 7813021
references.citation: Dev Cell. 2003 Mar;4(3):371-82
references.pmid: 12636918
references.citation: Science. 2003 Aug 15;301(5635):972-6
references.pmid: 12920301
references.citation: Nat Cell Biol. 2007 Feb;9(2):201-9
references.pmid: 17187062
references.citation: Breast Cancer Res. 2008;10(1):203
references.pmid: 18304381
references.citation: Dev Cell. 2001 Oct;1(4):467-75
references.pmid: 11703938
references.citation: Breast Cancer Res Treat. 1996;39(1):21-31
references.pmid: 8738603