Single-Cell Transcriptomes Distinguish Stem Cell State Changes and Lineage Specification Programs in Early Mammary...

Area of Science:

• Developmental Biology
• Genomics
• Cell Biology

Background:

• Mammary gland cells exhibit diverse gene expression patterns.
• Understanding mammary gland lineage specification and developmental kinetics is limited.

Purpose of the Study:

• To create a single-cell transcriptome atlas of mouse mammary development.
• To map cell states and identify fetal mammary stem cells (fMaSCs).

Main Methods:

• Single-cell RNA sequencing
• Transcriptome atlas generation
• Analysis of embryonic, postnatal, and adult mouse mammary tissue

Main Results:

• Chronology of transcriptionally and epigenetically distinct cell states mapped.
• Fetal mammary stem cells (fMaSCs) distinguished from precursors and progeny.
• fMaSCs exhibit balanced lineage factors and a transient metabolic signature.

Conclusions:

• Provides a resource for understanding mammary cell heterogeneity and differentiation kinetics.
• Identifies developmental correlates of tumorigenesis, including a metabolic signature in fMaSCs.
• Highlights the re-emergence of a metabolic gene signature in human breast cancers.