Both normal stem cells and at least some of the cancer cells must be able to self renew. The difference between a self renewing normal stem cell and a self renewing cancer cell is that unlike normal stem cells in which the total number of stem cells in a tissue is highly regulated and expansion beyond the normal level is restricted by genetic programs [6], there is a continuous expansion of self renewing cells in cancer resulting in the development of a tumor. There are 2 possible cells of origin for the self renewing cancer cells. First, it is possible that the cancers arise from normal stem cells that have lost the genetic constraints on self renewal. Next, it is possible that cancers arise from progenitor cells that have acquired the ability to self renew. Our laboratories have used single cell genomics to begin to define the cellular hierarchy of the normal human breast epithelium and de novo breast tumors. In this grant, we will use this technology in order to compare the cellular hierarchies of ER-,PR-, ERB-B2- (triple negative) breast tumors of different ethnicities to the cell types found in nonnal breast epithelium. This knowledge may lead to new insights into the treatment of breast cancer. The following specific aims will address those goals.
Specific Aim # 1: To use single cell genomics technology to define the cellular hierarchy of normal human epithelium.
Specific Aim #2 : To use single cell genomics technology to understand the cellular hierarchy of ER-PR-ERB-B2- (triple negative, basal cell) breast cancer in different racial groups.
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| Cai, Shang; Kalisky, Tomer; Sahoo, Debashis et al. (2017) A Quiescent Bcl11b High Stem Cell Population Is Required for Maintenance of the Mammary Gland. Cell Stem Cell 20:247-260.e5 |
| Song, Chun-Xiao; Yin, Senlin; Ma, Li et al. (2017) 5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages. Cell Res 27:1231-1242 |
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| Wu, Angela R; Neff, Norma F; Kalisky, Tomer et al. (2014) Quantitative assessment of single-cell RNA-sequencing methods. Nat Methods 11:41-6 |
| Adorno, Maddalena; Sikandar, Shaheen; Mitra, Siddhartha S et al. (2013) Usp16 contributes to somatic stem-cell defects in Down's syndrome. Nature 501:380-4 |
| Bockhorn, Jessica; Dalton, Rachel; Nwachukwu, Chika et al. (2013) MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nat Commun 4:1393 |
