ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR831/009/SRR8310489/SRR8310489.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR831/003/SRR8310493/SRR8310493.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR831/001/SRR8310491/SRR8310491.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR831/007/SRR8310487/SRR8310487.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR993/002/SRR9938472/SRR9938472.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR993/004/SRR9938474/SRR9938474.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR993/003/SRR9938473/SRR9938473.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR831/008/SRR8310488/SRR8310488.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR993/009/SRR9938469/SRR9938469.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR831/002/SRR8310492/SRR8310492.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR993/001/SRR9938471/SRR9938471.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR831/000/SRR8310490/SRR8310490.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR831/006/SRR8310486/SRR8310486.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR993/000/SRR9938470/SRR9938470.fastq.gzprimary200OKGenomicsCincinnati Children's Hospital Medical Centerhttps://www.ebi.ac.uk/ena/browser/view/PRJNA508501Mus musculusxref:PubMed:32840210xref:EuropePMC:PMC8419227Breast 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. Overall design: We compared the gene expression profile at single-cell level of four breast tumor models in mice.ENAfalseSingle-cell transcriptomic analysis of mammary tumors reveals distinct patterns of hierarchical and subtype heterogeneitySingle-cell transcriptomic analysis of mammary tumors reveals distinct patterns of hierarchical and subtype heterogeneity2025-09-242019-07-02PRJNA508501GSE1233661009032840210