Active Cells, Biochemistry & Physiology Genetics & Molecular Biology

Investigating epidermal cell fate plasticity in response to intrinsic and environmental perturbations

Funder Wellcome Charity-funded
Recipient organisation University of Cambridge
Funding Not disclosed
Period Oct 2025 — Sept 2028

In plain English

AI plain-English summary

Skin cells that have already committed to a specific role can reverse course and become flexible again, and this plasticity increases in aged skin. Dr. Maria Alcolea and colleagues have shown that cells marked by the protein KLF4 can lose their differentiation and rejoin the skin’s stem-like pool, a process that becomes more common in older tissue. This project asks whether the same plasticity occurs when skin is exposed to environmental pollutants, and whether it weakens the skin’s barrier and slows healing. The gap is clear: despite major genetic and physiological changes in aged and contaminated skin, almost no research has examined how cell plasticity contributes to these effects. If the work succeeds, it could reveal why older or polluted skin becomes fragile and heals poorly, pointing toward molecular targets for treatments that restore skin integrity. This is fundamental science—it will not produce a product tomorrow—but understanding the molecular regulators of plasticity could eventually inform therapies for chronic wounds, age-related skin fragility, or damage from urban pollution.

View original technical description
Skin is essential to homeostasis, as well as protection from injury and infection. Unsurprisingly, cellular plasticity to maintain barrier function is well established within the literature: hair follicle and sebaceous gland cells can dedifferentiate and contribute to wound healing in the interfollicular epidermis (IFE). Despite large genetic and physiological changes in aged and environmentally-exposed skin, very little research has been dedicated to the role of plasticity in these processes. Previous work by Dr. Maria Alcolea and colleagues identified KLF4 as a marker of a “differentiation-committed” population in skin and oesophagus. They demonstrated a novel role for KLF4 IFE cells, which can lose their commitment and recontribute to homeostasis in the IFE, through a process of plasticity that increased in prevalence in aged tissues. We hypothesise that this increased plasticity may also occur in aged and contaminated skin, causing tissue fragility and delayed healing. This project therefore aims to investigate how age and environmental (pollutant) perturbations influence epidermal cell fate plasticity. We hypothesise that such changes in plasticity may compromise skin integrity and contribute to an aging phenotype. To address this, we will examine how these perturbations affect cellular behaviour and identify the underlying molecular regulators.

View the original record at the funder ↗

Researchers

Elise Garcon (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

The impact of ageing on cell fate plasticity in squamous epithelial tissues
Identifying the impact of skin senescence through the lifecourse
Identifying quality control mechanisms in human skin and their role in the hallmarks of ageing
Investigating the consequences of primary and paracrine-driven secondary senescence for melanocyte function in 2D and 3D living skin equivalents
Evaluation of senolytic interventions in skin ageing

Original classification

PhD Studentship (Basic)

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.