Defining the principles governing cell fate decisions and plasticity in the adult epidermis

• Applicant: Dr. Paula Albu, Ph.D.
• Subject Area: Cell Biology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 585305580

The skin epidermis is a multilayered epithelium and a life-essential barrier maintained by the continuous turnover of stem cells. These stem cells reside within the basal layer and adapt to local cues by balancing self-renewing divisions and differentiation. This plasticity allows the epidermis to repair injuries and undergo tissue size changes. The precise potential of plasticity and underlying mechanisms remain poorly understood. Here, I will use the adult homeostatic epidermis and pre- and post-partum skin size adaptations as models to study the mechanisms of adaptation and plasticity in an injury-free setting. To identify cell fate transitions, in preliminary work, I discovered a promising marker, namely KLF4. I will define the cellular behaviors and molecular changes of pregnancy-related epidermal growth and regression (Objective 1). I will use quantitative tissue imaging coupled to spatial transcriptomics to identify when the first adaptive response to growth and regression occurs and uncover factors that regulate these cell transitions. To distinguish between short- and long-term adaptation I will assess the behavior and clonal dynamics of KLF4, a key candidate gene of plasticity, in control, pre-, and post-partum skins, at short and long intervals. These data will define the adaptive response to growth and regression at tissue, cell, and molecular scales. I will then proceed to dissect the cellular, molecular, and epigenetic mechanisms governing basal cell state transitions (Objective 2). I will quantify in vivo cell state dynamics by performing longitudinal intravital imaging of KLF4, Keratin 10 (differentiation), and AuroraB (proliferation) transcriptional reporters. I will test the role of KLF4 in cell state transitions through a mosaic gene deletion in the epidermis, coupled with immunostaining and intravital imaging. To uncover the molecular and epigenetic regulation of cell state transitions, I will perform single cell ATAC-sequencing of homeostatic skin, and integrate it with the RNA-sequencing data from Objective 1. The candidate regulators and/or markers of cell state transitions important for homeostatic and/or adaptive turnover will be validated using in vitro assays (short-term goal) and in vivo gestation paradigm (long-term goal). This project will set the foundation to understand the mechanisms across scales regulating adult adaptation and tissue turnover, with the long-term aim of aiding impaired adaptive responses such as during aging, after injury, or after sudden weight loss.

• DFG Programme: Position