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Single-cell analysis identifies TCF4 and ID3 as a molecular switch of mammary epithelial stem cell differentiation [mm_scRNAseq]

ABSTRACT: Mammary epithelial stem cells (MaSCs) generate the various types of epithelial cells that make up the mammary gland. However, the molecular mechanisms that regulate the differentiation of MaSCs are not well understood. We conducted a comprehensive scRNA-seq profiling of murine mammary epithelial cells, and identified a unique cell population that displays molecular characteristics of MaSCs. Upon further purification and detailed analysis, we discovered that these cells are not homogeneous. Instead, we identified three distinct subpopulations that represent the initial stages of lineage commitment. We inferred the developmental trajectory and found that one of these subpopulations represents bipotent MaSCs, from which luminal and basal lineages diverge. Using a network approach, we further identified E2-2 (Tcf4) and ID3 as potential molecular switches that could influence MaSC differentiation. Finally, we verified the existence of these novel MaSCs subpopulations in human breast tissue and examined their signatures in various breast cancer subtypes.

ORGANISM(S): Mus musculus

PROVIDER: GSE250111 | GEO | 2026/08/09

REPOSITORIES: GEO

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Single-cell analysis identifies TCF4 and ID3 as a molecular switch of mammary epithelial stem cell differentiation [hg_scRNAseq]

Project description:Mammary epithelial stem cells (MaSCs) generate the various types of epithelial cells that make up the mammary gland. However, the molecular mechanisms that regulate the differentiation of MaSCs are not well understood. We conducted a comprehensive scRNA-seq profiling of murine mammary epithelial cells, and identified a unique cell population that displays molecular characteristics of MaSCs. Upon further purification and detailed analysis, we discovered that these cells are not homogeneous. Instead, we identified three distinct subpopulations that represent the initial stages of lineage commitment. We inferred the developmental trajectory and found that one of these subpopulations represents bipotent MaSCs, from which luminal and basal lineages diverge. Using a network approach, we further identified E2-2 (Tcf4) and ID3 as potential molecular switches that could influence MaSC differentiation. Finally, we verified the existence of these novel MaSCs subpopulations in human breast tissue and examined their signatures in various breast cancer subtypes.

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