Impact of ageing on epidermal cell fate plasticity

Grantee: Maria Alcolea, Associate Professor, University of Cambridge

Amount: DKK 3,887,952

Grant category: Research Grants in open competition

Year: 2024

Geography: United Kingdom

Maria Alcolea’s project explores how the plasticity of skin cells is affected by aging. Maria Alcolea and her team will study the molecular pathways that modulate changes in cell behaviour throughout life. The ultimate aim is to identify new targets to improve tissue regeneration and delay the regenerative decline associated with human skin ageing.

The ability of epithelial cells to rewire their program of cell fate in response to tissue perturbations has emerged as a new paradigm in stem cell biology. This plasticity improves the efficiency of tissue repair by enabling differentiated/lineage committed cells to reacquire stem cell-like behavior in response to damage. However, despite obvious implications for skin regeneration, virtually nothing is known about how the plastic capacity of skin cells is affected by ageing, and whether this contributes to changes in the normal physiology of the epidermis at later stages in life.

Maria Alcolea’s project will investigate the impact of aging in skin cell fate plasticity by making use of a novel in vivo model that enables tracing the fate of epidermal cells from the earliest stages of commitment towards differentiation. Newly developed tools offers a unique opportunity to identify the mechanisms dictating epithelial cell fate plasticity and determine whether aged-associated changes in this process hold the key to understand why the regenerative capacity of our skin declines over time. She will combine the lab’s expertise in in vivo quantitative lineage tracing, single-cell RNA sequencing approaches, and mathematical network analysis. Observations made in in vivo mouse models will be compared to human skin using a novel 3D organ culture.

Maria Alcolea’s project may contribute significantly to the emerging field of epidermal cell plasticity and provide a benchmark for identifying potential targets to partially reduce/reverse skin ageing.