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Anstine et al. J Cancer Metastasis Treat 2019;5:50 I http://dx.doi.org/10.20517/2394-4722.2019.24 Page 13 of 16

while single cell sequencing technologies can provide high resolution maps of cellular states, they cannot
make definitive predictive connections to the resulting cellular fates. The use of newly developed technologies,
such as “CellTagging” that allow for early transcriptional statuses to be linked to cellular fates will allow
for a clearer understanding of epithelial lineage relationships within the mammary gland . Furthermore,
[108]
studies layering single cell technologies that assess transcriptional, epigenetic, and proteomic data within
the normal gland, primary tumor, and associated metastatic lesions should provide important information
regarding the extent of plasticity of primary and metastatic tumor cells that can be therapeutically leveraged
to promote differentiation of breast cancers into less malignant states.

DECLARATIONS
Authors’ contributions
Conceptualized and drafted the manuscript: Anstine LJ
Revised the manuscript for important intellectual content: Keri R

Availability of data and materials
Not applicable.

Financial support and sponsorship
None.

Conflicts of interest
Both authors declared that there are no conflicts of interest.

Ethical approval and consent to participate
Not applicable.

Consent for publication
Not applicable.

Copyright
© The Author(s) 2019.

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