Abstract
Although the existence of mammary stem cells has been suggested by serial transplantation studies in mice, their identification has been hindered by the lack of specific surface markers, and by the absence of suitable in vitro assays for testing stem cell properties: self-renewal and ability to generate differentiated progeny. We have developed an in vitro cultivation system that allows for propagation of human mammary epithelial cells (HMECs) in an undifferentiated state, based on their ability to proliferate in suspension, as nonadherent mammospheres. We demonstrate that nonadherent mammospheres are enriched in early progenitor/stem cells and able to differentiate along all three mammary epithelial lineages and to clonally generate complex functional structures in reconstituted 3D culture systems. Gene expression analysis of cells isolated from nonadherent mammospheres revealed overlapping genetic programs with other stem and progenitor cells and identified new markers that may be useful in the identification of mammary stem cells. The isolation and characterization of these stem cells should help elucidate the molecular pathways that govern normal mammary development and carcinogenesis.
References
53
Referenced
1,937
10.1073/pnas.0530291100
10.1186/bcr563
10.1016/S0092-8674(01)00409-3
10.1097/01.LAB.0000017371.72714.C5
/ Lab. Invest. / Common adult stem cells in the human breast give rise to glandular and myoepithelial cell lineages: A new cell biological concept. by Bocker (2002)10.1186/bcr321
10.1002/stem.200011
10.1016/0531-5565(71)90053-2
10.1023/A:1005942923757
10.4049/jimmunol.167.8.4747
10.1016/S0896-6273(01)00209-4
10.1006/dbio.2000.9611
10.1101/gad.952602
10.1016/S1534-5807(01)00064-8
10.1126/science.1073823
10.1002/(SICI)1097-0177(200006)218:2<235::AID-DVDY2>3.0.CO;2-G
10.1006/excr.2000.5013
10.1038/sj.onc.1205462
10.1242/dev.125.10.1921
/ Development / An entire functional mammary gland may comprise the progeny from a single cell. by Kordon (1998)10.1002/jcp.10030
10.1038/sj.leu.2402684
10.1073/pnas.82.5.1419
10.1016/S0092-8674(00)81867-X
10.1038/35065016
{'key': '2021111519023238000_17.10.1253.24', 'first-page': '2817', 'article-title': 'Division of labor among the α6β4 integrin β1 integrins, and an E3 laminin receptor to signal morphogenesis and β-casein expression in mammary epithelial cells.', 'volume': '10', 'author': 'Muschler', 'year': '1999', 'journal-title': 'Mol. Biol.'}
/ Mol. Biol. / Division of labor among the α6β4 integrin β1 integrins, and an E3 laminin receptor to signal morphogenesis and β-casein expression in mammary epithelial cells. by Muschler (1999)10.1016/0014-4827(85)90556-7
10.1073/pnas.89.19.9064
10.1126/science.1072530
10.1038/35102167
10.1006/dbio.1996.0090
10.1038/35054579
-
Rudland P.S. Barraclough R. Fernig D.G. Smith J.A. (1997) Mammary stem cells in normal development and cancer. in Stem Cells, ed Potten C.S. (Academic Press, San Diego, CA), pp 147–232.
(
10.1016/B978-012563455-7/50008-8
) 10.1182/blood.V99.2.507
10.1016/S0166-2236(99)01416-2
10.1242/dev.128.16.3117
/ Development / The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. by Simian (2001)10.1002/1097-0029(20010115)52:2<190::AID-JEMT1005>3.0.CO;2-O
/ Microscopy Res. Tech. / Mammary epithelial stem cells. by Smith (2001)10.1007/BF02623435
/ In Vitro Cell. Dev. Biol. / A simplified method for passage and long-term growth of human mammary epithelial cells. by Soule (1986)10.1111/j.1432-0436.1998.00201.x
10.1023/A:1010615124301
10.1182/blood.V96.6.2125
/ Blood / Hoechst dye efflux reveals a novel CD7+CD34− lymphoid progenitor in human umbilical cord blood. by Storms (2000)10.1038/35077219
10.1073/pnas.131200898
10.1006/dbio.1998.8863
{'key': '2021111519023238000_17.10.1253.43', 'first-page': '3028', 'article-title': 'Mammaglobin expression in primary, metastatic, and occult breast cancer.', 'volume': '59', 'author': 'Watson', 'year': '1999', 'journal-title': 'Cancer Res.'}
/ Cancer Res. / Mammaglobin expression in primary, metastatic, and occult breast cancer. by Watson (1999)10.1023/A:1018781325716
10.1016/S0166-2236(96)10035-7
10.1016/S0092-8674(00)81692-X
10.1006/dbio.2002.0625
10.1126/science.1067431
10.1093/nar/30.10.e48
10.1002/1097-0290(20000920)69:6<607::AID-BIT4>3.3.CO;2-6
{'key': '2021111519023238000_17.10.1253.51', 'first-page': '3640', 'article-title': 'MCF-10A-NeoST: A new cell system for studying cell–ECM and cell–cell interactions in breast cancer.', 'volume': '7', 'author': 'Zantek', 'year': '2001', 'journal-title': 'Clin. Cancer Res.'}
/ Clin. Cancer Res. / MCF-10A-NeoST: A new cell system for studying cell–ECM and cell–cell interactions in breast cancer. by Zantek (2001)10.1006/exnr.2000.7425
10.1038/nm0901-1028
Dates
Type | When |
---|---|
Created | 22 years, 3 months ago (May 16, 2003, 5:20 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 15, 2021, 10:11 p.m.) |
Indexed | 19 hours, 44 minutes ago (Aug. 21, 2025, 1:40 p.m.) |
Issued | 22 years, 3 months ago (May 15, 2003) |
Published | 22 years, 3 months ago (May 15, 2003) |
Published Online | 22 years, 3 months ago (May 15, 2003) |
Published Print | 22 years, 3 months ago (May 15, 2003) |
@article{Dontu_2003, title={In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells}, volume={17}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.1061803}, DOI={10.1101/gad.1061803}, number={10}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Dontu, Gabriela and Abdallah, Wissam M. and Foley, Jessica M. and Jackson, Kyle W. and Clarke, Michael F. and Kawamura, Mari J. and Wicha, Max S.}, year={2003}, month=may, pages={1253–1270} }