Our group has developed a powerful organoid assay for modeling human mammary gland development and maturation. As a tissue source for our organoid assay, we collect primary cells from normal human breast tissue and milk. Surprisingly, human milk contains thousands of viable, actively proliferating mammary epithelial cells that can be cultured as organoids. By single-cell RNA-sequencing, we discovered that cells from human milk represent a wide spectrum of differentiation states. Comparing primary cells from the resting mammary gland with milk cells provides us with unique insights into human mammary gland maturation and lactation. We are especially interested in understanding fundamental mechanisms of regeneration and lineage plasticity that have recently begun to be implicated as fundamental hallmarks of mammary gland biology. We speculate that such mechanisms might also be subverted during breast cancer progression and provide explanations for the immense heterogeneity and complexity of this disease. Based on these findings and considerations, in this project, you will combine epigenetic profiling with functional genomics and organoid culture to gain insights into the enhancer landscape in the resting and lactating human mammary gland. Your goal is to uncover fundamental mechanisms of how lineage identity is maintained and re-assigned during distinct functional states within the human mammary gland.

Related literature:

Britschgi A, et al. (2017), The Hippo kinases LATS1/2 control human breast cell fate via crosstalk with Erα. Nature, 541(7638), 541-545

Linnemann JR, et al. (2015), Quantification of regenerative potential in primary human mammary epithelial cells. Development, 142, 3239-3251

Schmidt JM, et al. (2015), Stem cell-like properties and epithelial plasticity arise as stable traits after transient Twist1 activation. Cell Reports, Vol. 10(2), 131-139

Scheel C, et al. (2011) Paracrine and Autocrine Signals Induce and Maintain Mesenchymal and Stem Cell States in the Breast. Cell, 145(6)