First Author | Yeo SK | Year | 2020 |
Journal | Elife | Volume | 9 |
PubMed ID | 32840210 | Mgi Jnum | J:308026 |
Mgi Id | MGI:6727660 | Doi | 10.7554/eLife.58810 |
Citation | Yeo SK, et al. (2020) Single-cell RNA-sequencing reveals distinct patterns of cell state heterogeneity in mouse models of breast cancer. Elife 9:e58810 |
abstractText | Breast cancer stem cells (BCSCs) contribute to intra-tumoral heterogeneity and therapeutic resistance. However, the binary concept of universal BCSCs co-existing with bulk tumor cells is over-simplified. Through single-cell RNA-sequencing, we found that Neu, PyMT and BRCA1-null mammary tumors each corresponded to a spectrum of minimally overlapping cell differentiation states without a universal BCSC population. Instead, our analyses revealed that these tumors contained distinct lineage-specific tumor propagating cells (TPCs) and this is reflective of the self-sustaining capabilities of lineage-specific stem/progenitor cells in the mammary epithelial hierarchy. By understanding the respective tumor hierarchies, we were able to identify CD14 as a TPC marker in the Neu tumor. Additionally, single-cell breast cancer subtype stratification revealed the co-existence of multiple breast cancer subtypes within tumors. Collectively, our findings emphasize the need to account for lineage-specific TPCs and the hierarchical composition within breast tumors, as these heterogenous sub-populations can have differential therapeutic susceptibilities. |