Molecular and cellular mechanisms controlling self-renewal and regeneration of skin

We aim to answer fundamental questions about tissue homeostasis, repair and regeneration, by uncovering regulatory mechanisms at the cellular and molecular level that dictate stem cell renewal, cell-fate specification and differentiation.

We focus on the skin, where renewal of the outer epithelial layer and the cycling hair follicles depend on continuously ongoing multi-lineage differentiation processes from resident tissue stem cells.

Building upon the single-cell characterization of skin cell types and their genetic programs from my lab (Joost et al. 2016, 2018, 2020), we will in this research program first investigate the triggers for epidermal stem cell activation and differentiation, which to date are unknown.

Specifically, we will investigate how tissue-resident immune cells regulate epidermal tissue turnover, as well as utilize single-cell transcriptomics with the ability to separate new and pre-existing RNAs (NASC-seq) to discover pioneering factors that push stem cells into differentiation.

Secondly, we will extend our recent work on inducing de novo hair follicles towards human skin, which is of worldwide importance for patients with skin replacement needs.

To achieve these aims, we combine scRNA-seq, advanced mouse models, slow-release in vivo delivery systems, multiplex in situ imaging, NASC-seq and organoid culture, to determine the boundary of stem cell plasticity and reversibility, with the long-term aim to re-activate tissue stem cells in a controlled manner.