Mammary gland lineage identity and multi-omics landscapes

This project focuses on defining how epithelial lineage identity is established, maintained, and dynamically remodelled across different developmental stages of the mammary gland.

Although single-cell RNA sequencing has previously characterised cellular heterogeneity in the mammary gland, robust lineage-specific expression and chromatin profiles require purified cell populations. In this study, transgenic mice specifically labelling ER-positive luminal cells were combined with cell-surface marker isolation strategies to purify the three major mammary epithelial lineages: basal cells, ER-positive luminal cells, and ER-negative luminal cells.

Using bulk RNA-seq, ATAC-seq, and computational cell–cell communication analyses, this study generated a comprehensive transcriptional and chromatin landscape of mammary gland epithelial lineages across puberty, adulthood, and pregnancy.

Integrative multi-omics analyses identified conserved and stage-specific transcriptional programmes, chromatin accessibility landscapes, ligand–receptor interactions, and transcription factor regulatory networks associated with each epithelial lineage throughout life. Importantly, this approach enabled detailed profiling of the rare ER-positive luminal population during pregnancy.

Together, this study provides a systems-level resource describing how epithelial lineage identity, gene regulatory networks, and intercellular communication are dynamically regulated throughout mammary gland development and physiological remodelling.

Publication

Cell type and stage specific transcriptional, chromatin and cell-cell communication landscapes in the mammary gland
Heliyon (2023)
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Highlights

• Defined transcriptional and chromatin landscapes of major mammary epithelial lineages.
• Characterised basal, ER-positive luminal, and ER-negative luminal epithelial identities.
• Identified lineage-specific transcription factors and regulatory programmes across development.
• Revealed stage-specific ligand–receptor interactions and epithelial communication networks.
• Integrated bulk RNA-seq and ATAC-seq analyses across puberty, adulthood, and pregnancy.
• Generated a comprehensive multi-omics resource for mammary gland epithelial biology.

My contribution

I contributed to the computational analysis of bulk RNA-seq and ATAC-seq datasets, including chromatin accessibility analysis, transcription factor enrichment, lineage-specific gene programme identification, and cell–cell communication analyses. My work also involved integrating transcriptional and chromatin datasets to characterise developmental and lineage-specific regulatory landscapes in the mammary gland.