DCS Next-Gen Seminar: Bethan Lloyd-Lewis
| Dates: | 13 November 2023 |
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| Times: | 15:00 - 16:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Biology, Medicine and Health |
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DCS Next-Gen Seminar Series -
Monday 13th November
15:00 - 16:00 GMT
OCRB Lecture Theatre
Dr Bethan Lloyd-Lewis
The University of Bristol
"Dynamic decisions: Mammary cell fate during development and disease"
During development, stem and progenitor cells give rise to specialised cell types to build complex three-dimensional tissues. Adult stem and progenitor cells also function to replenish cells lost to tissue turnover or injury. In certain contexts, such as in response to stem cell depletion or pre-cancerous mutations, some epithelial cell types are able to change their fate (defined as cellular plasticity). To maintain tissue homeostasis these processes must be tightly controlled, as they can be hijacked during the initial stages of some cancers. Focusing on the breast, we study the biological mechanisms regulating stem cell fate and plasticity during mammary tissue development, and the changes that occur during the earliest stages of breast cancer.
The mammary epithelium originates from multipotent stem cells, which are progressively replaced by distinct pools of unipotent progenitors by birth. However, our understanding of this process remains limited. To address this, we used scRNA-sequencing across embryonic development to reconstruct the differentiation trajectories of multipotent mammary stem cells towards distinct lineages. Our data revealed that cell fate commitment occurs surprisingly early in mammogenesis at E15.5, which coincides with the epithelial remodelling that drives the first mammary branching event. Alongside, we determined that tissue positional cues underpin cell fate specification during embryonic ductal morphogenesis. We also identified mesenchymal-produced FGF10 as a critical driver of embryonic mammary branching. Collectively, these data provide new insights into the spatiotemporal signals underlying mammary lineage specification, and the paracrine interactions between epithelial and mesenchymal cells that guide mammary branching morphogenesis. Our findings may have important implications towards advancing understanding of how reactivation of embryonic developmental programs can contribute to breast cancer.
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