REFERENCES
1. Wiseman BS, Werb Z. Stromal effects on mammary gland development and breast cancer. Science 2002;296:1046-9.
2. Hu GF, Li LZ, Xu W. Extracellular matrix in mammary gland development and breast cancer progression. Frontiers in Laboratory Medicine 2017;1:36-9.
3. Watson CJ, Khaled WT. Mammary development in the embryo and adult: a journey of morphogenesis and commitment. Development 2008;135:995-1003.
4. Gjorevski N, Nelson CM. Integrated morphodynamic signalling of the mammary gland. Nat Rev Mol Cell Biol 2011;12:581-93.
5. Richert MM, Schwertfeger KL, Ryder JW, Anderson SM. An atlas of mouse mammary gland development. J Mammary Gland Biol Neoplasia 2000;5:227-41.
6. Wagner KU, Boulanger CA, Henry MD, Sgagias M, Hennighausen L, et al. An adjunct mammary epithelial cell population in parous females: its role in functional adaptation and tissue renewal. Development 2002;129:1377-86.
7. Smith GH. Experimental mammary epithelial morphogenesis in an in vivo model: evidence for distinct cellular progenitors of the ductal and lobular phenotype. Breast Cancer Res Treat 1996;39:21-31.
8. Fu N, Lindeman GJ, Visvader JE. The mammary stem cell hierarchy. Curr Top Dev Biol 2014;107:133-60.
9. Rodilla V, Fre S. Cellular plasticity of mammary epithelial cells underlies heterogeneity of breast cancer. Biomedicines 2018;6:E103.
10. Visvader JE, Stingl J. Mammary stem cells and the differentiation hierarchy: current status and perspectives. Genes Dev 2014;28:1143-58.
11. Bach K, Pensa S, Grzelak M, Hadfield J, Adams DJ, et al. Differentiation dynamics of mammary epithelial cells revealed by single-cell RNA sequencing. Nat Commun 2017;8:2128.
12. Giraddi RR, Chung CY, Heinz RE, Balcioglu O, Novotny M, et al. Single-cell transcriptomes distinguish stem cell state changes and lineage specification programs in early mammary gland development. Cell Rep 2018;24:1653-1666.e7.
13. Sun H, Miao Z, Zhang X, Chan UI, Su SM, et al. Single-cell RNA-Seq reveals cell heterogeneity and hierarchy within mouse mammary epithelia. J Biol Chem 2018;293:8315-29.
14. Nguyen QH, Pervolarakis N, Blake K, Ma D, Davis RT, et al. Profiling human breast epithelial cells using single cell RNA sequencing identifies cell diversity. Nat Commun 2018;9:2028.
15. Deome KB, Faulkin LJ Jr, Bern HA, Blair PB. Development of mammary tumors from hyperplastic alveolar nodules transplanted into gland-free mammary fat pads of female C3H mice. Cancer Res 1959;19:515-20.
16. Daniel CW, De Ome KB, Young JT, Blair PB, Faulkin LJ Jr. The in vivo life span of normal and preneoplastic mouse mammary glands: a serial transplantation study. Proc Natl Acad Sci U S A 1968;61:53-60.
17. Hoshino K. Morphogenesis and growth potentiality of mammary glands in mice. I. Transplantability and growth potentiality of mammary tissue of virgin mice. J Natl Cancer Inst 1962;29:835-51.
18. Smith GH, Gallahan D, Zwiebel JA, Freeman SM, Bassin RH, et al. Long-term in vivo expression of genes introduced by retrovirus-mediated transfer into mammary epithelial cells. J Virol 1991;65:6365-70.
19. Smith GH, Medina D. A morphologically distinct candidate for an epithelial stem cell in mouse mammary gland. J Cell Sci 1988;90:173-83.
20. Young LJ, Medina D, DeOme KB, Daniel CW. The influence of host and tissue age on life span and growth rate of serially transplanted mouse mammary gland. Exp Gerontol 1971;6:49-56.
21. Kordon EC, Smith GH. An entire functional mammary gland may comprise the progeny from a single cell. Development 1998;125:1921-30.
22. Shackleton M, Vaillant F, Simpson KJ, Stingl J, Smyth GK, et al. Generation of a functional mammary gland from a single stem cell. Nature 2006;439:84-8.
23. Stingl J, Eirew P, Ricketson I, Shackleton M, Vaillant F, et al. Purification and unique properties of mammary epithelial stem cells. Nature 2006;439:993-7.
24. Shehata M, Teschendorff A, Sharp G, Novcic N, Russell IA, et al. Phenotypic and functional characterisation of the luminal cell hierarchy of the mammary gland. Breast Cancer Res 2012;14:R134.
25. Sleeman KE, Kendrick H, Ashworth A, Isacke CM, Smalley MJ. CD24 staining of mouse mammary gland cells defines luminal epithelial, myoepithelial/basal and non-epithelial cells. Breast Cancer Res 2006;8:R7.
26. Bai L, Rohrschneider LR. s-SHIP promoter expression marks activated stem cells in developing mouse mammary tissue. Genes Dev 2010;24:1882-92.
27. Plaks V, Brenot A, Lawson DA, Linnemann JR, Van Kappel EC, et al. Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis. Cell Rep 2013;3:70-8.
28. Rios AC, Fu NY, Lindeman GJ, Visvader JE. In situ identification of bipotent stem cells in the mammary gland. Nature 2014;506:322-7.
29. de Visser KE, Ciampricotti M, Michalak EM, Tan DW, Speksnijder EN, et al. Developmental stage-specific contribution of LGR5(+) cells to basal and luminal epithelial lineages in the postnatal mammary gland. J Pathol 2012;228:300-9.
30. Badders NM, Goel S, Clark RJ, Klos KS, Kim S, et al. The Wnt receptor, Lrp5, is expressed by mouse mammary stem cells and is required to maintain the basal lineage. PLoS One 2009;4:e6594.
31. Zeng YA, Nusse R. Wnt proteins are self-renewal factors for mammary stem cells and promote their long-term expansion in culture. Cell Stem Cell 2010;6:568-77.
32. Spike BT, Engle DD, Lin JC, Cheung SK, La J, et al. A mammary stem cell population identified and characterized in late embryogenesis reveals similarities to human breast cancer. Cell Stem Cell 2012;10:183-97.
33. Wang D, Cai C, Dong X, Yu QC, Zhang XO, et al. Identification of multipotent mammary stem cells by protein C receptor expression. Nature 2015;517:81-4.
34. Van Keymeulen A, Rocha AS, Ousset M, Beck B, et al. Distinct stem cells contribute to mammary gland development and maintenance. Nature 2011;479:189-93.
35. Davis FM, Lloyd-Lewis B, Harris OB, Kozar S, Winton DJ, et al. Single-cell lineage tracing in the mammary gland reveals stochastic clonal dispersion of stem/progenitor cell progeny. Nat Commun 2016;7:13053.
36. Wuidart A, Ousset M, Rulands S, Simons BD, Van Keymeulen A, et al. Quantitative lineage tracing strategies to resolve multipotency in tissue-specific stem cells. Genes Dev 2016;30:1261-77.
37. Boulanger CA, Wagner KU, Smith GH. Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGF-beta1 expression. Oncogene 2005;24:552-60.
38. van Amerongen R, Bowman AN, Nusse R. Developmental stage and time dictate the fate of Wnt/beta-catenin-responsive stem cells in the mammary gland. Cell Stem Cell 2012;11:387-400.
39. Song W, Wang R, Jiang W, Yin Q, Peng G, et al. Hormones induce the formation of luminal-derived basal cells in the mammary gland. Cell Res 2019; doi: 10.1038/s41422-018-0137-0.
40. Morris RJ, Liu Y, Marles L, Yang Z, Trempus C, et al. Capturing and profiling adult hair follicle stem cells. Nat Biotechnol 2004;22:411-7.
41. Rodriguez-Fraticelli AE, Wolock SL, Weinreb CS, Panero R, Patel SH, et al. Clonal analysis of lineage fate in native haematopoiesis. Nature 2018;553:212-6.
42. Rios AC, Fu NY, Cursons J, Lindeman GJ, Visvader JE. The complexities and caveats of lineage tracing in the mammary gland. Breast Cancer Res 2016;18:116.
43. Shehata M, van Amerongen R, Zeeman AL, Giraddi RR, Stingl J. The influence of tamoxifen on normal mouse mammary gland homeostasis. Breast Cancer Res 2014;16:411.
44. Yang X, Wang H, Jiao B. Mammary gland stem cells and their application in breast cancer. Oncotarget 2017;8:10675-91.
45. Lim E, Wu D, Pal B, Bouras T, Asselin-Labat ML, et al. Transcriptome analyses of mouse and human mammary cell subpopulations reveal multiple conserved genes and pathways. Breast Cancer Res 2010;12:R21.
46. Trejo CL, Luna G, Dravis C, Spike BT, Wahl GM. Lgr5 is a marker for fetal mammary stem cells, but is not essential for stem cell activity or tumorigenesis. NPJ Breast Cancer 2017;3:16.
47. Shi XS, Chakraborty P, Chaudhuri A. Unmasking tumor heterogeneity and clonal evolution by single-cell analysis. J Cancer Metastasis Treat 2018;4:47.
48. Eberwine J, Yeh H, Miyashiro K, Cao Y, Nair S, et al. Analysis of gene expression in single live neurons. Proc Natl Acad Sci U S A 1992;89:3010-4.
49. Cano-Gauci DF, Lualdi JC, Ouellette AJ, Brady G, Iscove NN, et al. In vitro cDNA amplification from individual intestinal crypts: a novel approach to the study of differential gene expression along the crypt-villus axis. Exp Cell Res 1993;208:344-9.
50. Svensson V, Vento-Tormo R, Teichmann SA. Exponential scaling of single-cell RNA-seq in the past decade. Nat Protoc 2018;13:599-604.
51. Kuipers J, Jahn K, Beerenwinkel N. Advances in understanding tumour evolution through single-cell sequencing. Biochim Biophys Acta Rev Cancer 2017;1867:127-38.
52. Wuidart A, Sifrim A, Fioramonti M, Matsumura S, Brisebarre A, et al. Early lineage segregation of multipotent embryonic mammary gland progenitors. Nat Cell Biol 2018;20:666-76.
53. Pal B, Chen Y, Vaillant F, Jamieson P, Gordon L, et al. Construction of developmental lineage relationships in the mouse mammary gland by single-cell RNA profiling. Nat Commun 2017;8:1627.
54. Wang C, Christin JR, Oktay MH, Guo W. Lineage-biased stem cells maintain estrogen-receptor-positive and -negative mouse mammary luminal lineages. Cell Rep 2017;18:2825-35.
55. Van Keymeulen A, Fioramonti M, Centonze A, Bouvencourt G, Achouri Y, et al. Lineage-restricted mammary stem cells sustain the development, homeostasis, and regeneration of the estrogen receptor positive lineage. Cell Rep 2017;20:1525-32.
56. Cai S, Kalisky T, Sahoo D, Dalerba P, Feng W, et al. A quiescent Bcl11b high stem cell population is required for maintenance of the mammary gland. Cell Stem Cell 2017;20:247-60.e5.
57. Fu NY, Rios AC, Pal B, Law CW, Jamieson P, et al. Identification of quiescent and spatially restricted mammary stem cells that are hormone responsive. Nat Cell Biol 2017;19:164-76.
58. Dravis C, Chung CY, Lytle NK, Herrera-Valdez J, Luna G, et al. Epigenetic and transcriptomic profiling of mammary gland development and tumor models disclose regulators of cell state plasticity. Cancer Cell 2018;34:466-82.e6.
59. Gu B, Sun P, Yuan Y, Moraes RC, Li A, et al. Pygo2 expands mammary progenitor cells by facilitating histone H3 K4 methylation. J Cell Biol 2009;185:811-26.
60. Liu S, Dontu G, Mantle ID, Patel S, Ahn NS, et al. Hedgehog signaling and Bmi-1 regulate self-renewal of normal and malignant human mammary stem cells. Cancer Res 2006;66:6063-71.
61. Pietersen AM, Evers B, Prasad AA, Tanger E, Cornelissen-Steijger P, et al. Bmi1 regulates stem cells and proliferation and differentiation of committed cells in mammary epithelium. Curr Biol 2008;18:1094-9.
62. Pal B, Bouras T, Shi W, Vaillant F, Sheridan JM, et al. Global changes in the mammary epigenome are induced by hormonal cues and coordinated by Ezh2. Cell Rep 2013;3:411-26.
63. Hoenerhoff MJ, Chu I, Barkan D, Liu ZY, Datta S, et al. BMI1 cooperates with H-RAS to induce an aggressive breast cancer phenotype with brain metastases. Oncogene 2009;28:3022-32.
64. Paranjape AN, Balaji SA, Mandal T, Krushik EV, Nagaraj P, et al. Bmi1 regulates self-renewal and epithelial to mesenchymal transition in breast cancer cells through Nanog. BMC Cancer 2014;14:785.
65. Moore HM, Gonzalez ME, Toy KA, Cimino-Mathews A, Argani P, et al. EZH2 inhibition decreases p38 signaling and suppresses breast cancer motility and metastasis. Breast Cancer Res Treat 2013;138:741-52.
66. Crea F, Fornaro L, Bocci G, Sun L, Farrar WL, et al. EZH2 inhibition: targeting the crossroad of tumor invasion and angiogenesis. Cancer Metastasis Rev 2012;31:753-61.
67. Lilja AM, Rodilla V, Huyghe M, Hannezo E, Landragin C, et al. Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain long-term plasticity in the embryonic mammary gland. Nat Cell Biol 2018;20:677-87.
69. Laurenti E, Gottgens B. From haematopoietic stem cells to complex differentiation landscapes. Nature 2018;553:418-26.
71. Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol 2011;5:5-23.
72. Prat A, Parker JS, Karginova O, Fan C, Livasy C, et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res 2010;12:R68.
73. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001;98:10869-74.
74. Neve RM, Chin K, Fridlyand J, Yeh J, Baehner FL, et al. A collection of breast cancer cell lines for the study of functionally distinct cancer subtypes. Cancer Cell 2006;10:515-27.
75. Easwaran H, Tsai HC, Baylin SB. Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol Cell 2014;54:716-27.
76. Lim E, Vaillant F, Wu D, Forrest NC, Pal B, et al. Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 2009;15:907-13.
77. Molyneux G, Geyer FC, Magnay FA, McCarthy A, Kendrick H, et al. BRCA1 basal-like breast cancers originate from luminal epithelial progenitors and not from basal stem cells. Cell Stem Cell 2010;7:403-17.
78. Herschkowitz JI, Simin K, Weigman VJ, Mikaelian I, Usary J, et al. Identification of conserved gene expression features between murine mammary carcinoma models and human breast tumors. Genome Biol 2007;8:R76.
79. Proia TA, Keller PJ, Gupta PB, Klebba I, Jones AD, et al. Genetic predisposition directs breast cancer phenotype by dictating progenitor cell fate. Cell Stem Cell 2011;8:149-63.
80. Karaayvaz M, Cristea S, Gillespie SM, Patel AP, Mylvaganam R, et al. Unravelling subclonal heterogeneity and aggressive disease states in TNBC through single-cell RNA-seq. Nat Commun 2018;9:3588.
81. Ferrari A, Sertier AS, Vincent-Salomon A, Pivot X, Pauporte I, et al. A phenotypic and mechanistic perspective on heterogeneity of HER2-positive breast cancers. Mol Cell Oncol 2016;3:e1232186.
82. Vaillant F, Asselin-Labat ML, Shackleton M, Forrest NC, Lindeman GJ, et al. The mammary progenitor marker CD61/beta3 integrin identifies cancer stem cells in mouse models of mammary tumorigenesis. Cancer Res 2008;68:7711-7.
83. Wang Y, Krivtsov AV, Sinha AU, North TE, Goessling W, et al. The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in AML. Science 2010;327:1650-3.
84. Thompson EG, Fares H, Dixon K. BRCA1 requirement for the fidelity of plasmid DNA double-strand break repair in cultured breast epithelial cells. Environ Mol Mutagen 2012;53:32-43.
85. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 2012;21:283-96.
86. Chung W, Eum HH, Lee HO, Lee KM, Lee HB, et al. Single-cell RNA-seq enables comprehensive tumour and immune cell profiling in primary breast cancer. Nat Commun 2017;8:15081.
87. Banerji S, Cibulskis K, Rangel-Escareno C, Brown KK, Carter SL, et al. Sequence analysis of mutations and translocations across breast cancer subtypes. Nature 2012;486:405-9.
88. Ellis MJ, Perou CM. The genomic landscape of breast cancer as a therapeutic roadmap. Cancer Discov 2013;3:27-34.
89. Shipitsin M, Polyak K. The cancer stem cell hypothesis: in search of definitions, markers, and relevance. Lab Invest 2008;88:459-63.
90. Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008;133:704-15.
91. Sin WC, Lim CL. Breast cancer stem cells-from origins to targeted therapy. Stem Cell Investig 2017;4:96.
92. Guo W, Keckesova Z, Donaher JL, Shibue T, Tischler V, et al. Slug and Sox9 cooperatively determine the mammary stem cell state. Cell 2012;148:1015-28.
93. Psaila B, Lyden D. The metastatic niche: adapting the foreign soil. Nat Rev Cancer 2009;9:285-93.
94. Chaffer CL, Marjanovic ND, Lee T, Bell G, Kleer CG, et al. Poised chromatin at the ZEB1 promoter enables breast cancer cell plasticity and enhances tumorigenicity. Cell 2013;154:61-74.
95. Lau EY, Ho NP, Lee TK. Cancer stem cells and their microenvironment: biology and therapeutic implications. Stem Cells Int 2017;2017:3714190.
96. Paget S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev 1989;8:98-101.
97. Huo CW, Hill P, Chew G, Neeson PJ, Halse H, et al. High mammographic density in women is associated with protumor inflammation. Breast Cancer Res 2018;20:92.
98. Mentoor I, Engelbrecht AM, van Jaarsveld PJ, Nell T. Chemoresistance: intricate interplay between breast tumor cells and adipocytes in the tumor microenvironment. Front Endocrinol (Lausanne) 2018;9:758.
99. Martinson HA, Jindal S, Durand-Rougely C, Borges VF, Schedin P. Wound healing-like immune program facilitates postpartum mammary gland involution and tumor progression. Int J Cancer 2015;136:1803-13.
100. Bruno RD, Smith GH. Reprogramming non-mammary and cancer cells in the developing mouse mammary gland. Semin Cell Dev Biol 2012;23:591-8.
101. Bruno RD, Boulanger CA, Rosenfield SM, Anderson LH, Lydon JP, et al. Paracrine-rescued lobulogenesis in chimeric outgrowths comprising progesterone-receptor-null mammary epithelium and redirected wild-type testicular cells. J Cell Sci 2014;127:27-32.
102. Boulanger CA, Bruno RD, Rosu-Myles M, Smith GH. The mouse mammary microenvironment redirects mesoderm-derived bone marrow cells to a mammary epithelial progenitor cell fate. Stem Cells Dev 2012;21:948-54.
103. Bruno RD, Fleming JM, George AL, Boulanger CA, Schedin P, et al. Mammary extracellular matrix directs differentiation of testicular and embryonic stem cells to form functional mammary glands in vivo. Sci Rep 2017;7:40196.
104. Boulanger CA, Bruno RD, Mack DL, Gonzales M, Castro NP, et al. Embryonic stem cells are redirected to non-tumorigenic epithelial cell fate by interaction with the mammary microenvironment. PLoS One 2013;8:e62019.
105. Barcellos-Hoff MH, Ravani SA. Irradiated mammary gland stroma promotes the expression of tumorigenic potential by unirradiated epithelial cells. Cancer Res 2000;60:1254-60.
106. Maffini MV, Calabro JM, Soto AM, Sonnenschein C. Stromal regulation of neoplastic development: age-dependent normalization of neoplastic mammary cells by mammary stroma. Am J Pathol 2005;167:1405-10.
107. Casey AE, Sinha A, Singhania R, Livingstone J, Waterhouse P, et al. Mammary molecular portraits reveal lineage-specific features and progenitor cell vulnerabilities. J Cell Biol 2018;217:2951-74.
