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Single-cell RNA-sequencing reveals distinct patterns of cell state heterogeneity in mouse models of breast cancer.

ABSTRACT: 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.

SUBMITTER: Yeo SK

PROVIDER: S-EPMC7447441 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Single-cell RNA-sequencing reveals distinct patterns of cell state heterogeneity in mouse models of breast cancer.

Yeo Syn Kok SK Zhu Xiaoting X Okamoto Takako T Hao Mingang M Wang Cailian C Lu Peixin P Lu Long Jason LJ Guan Jun-Lin JL

eLife 20200825

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 ...[more]

PMID: 32840210

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Single-cell RNA-sequencing reveals distinct patterns of cell state heterogeneity in mouse models of breast cancer.

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Single-cell RNA-sequencing reveals distinct patterns of cell state heterogeneity in mouse models of breast cancer.

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