Background

Stem cells are unique cells within a body. They are characterized by the ability to renew themselves and to differentiate into a diverse range of specialized cell types. During development, tissue specific stem cells form all the necessary lineages to form a functional tissue. In adulthood, these stem cells allow continuous regeneration and repair of the tissue.

 

The skin as a stem cell research system  

The skin is the largest organ of our body. The primary role of the skin is to protect our internal organs from external stressors such as sunlight, infection or dehydration. In addition to its barrier function, the skin is also a sensory organ, capable of perceiving heat, pain and subtle texture sensations.

 

The skin consists of two compartments: outer epidermis and inner dermis (Figure 1). These two layers are separated by a basement membrane. The epidermis is a stratified epithelium. The innermost, or basal layer of the epidermis contains epidermal stem cells (EpSCs). During development, EpSCs undergo a precise differentiation process resulting in stratification, and the cells at the uppermost layers lose their nuclei and form a protective barrier. At the same time, EpSCs also contribute to the hair follicles, sebaceous glands and sensory Merkel cells. Postnatally, the basal layer continuously replenishes the epidermal barrier. Separate pools of hair follicle and sebaceous glands specific stem cells maintain these appendages in the adult, under homeostasis or stress conditions.

 

The variety of cell lineages, the regenerative features, the availability of genetic tools to perform in vivo loss- and gain-of function studies, the existence of molecular markers of stem cells and their differentiated progenies, as well as the possibility to purify and to culture stem cells make the skin a unique model system to study stem cell function and behavior.

 

Epigenetics in stem cell control

Identification of the molecular mechanisms that control self-renewal and differentiation of stem cells is fundamentally important to understand tissue development and homeostasis, as well as the progression of  tissue disorders including cancer. Several lines of evidence indicate the importance of epigenetic regulators in control of these processes. Our long-term interest is to elucidate the roles of epigenetics regulators in stem cell control using skin as a model system. We are interested: 1) Discovering whether the epigenetic machinery controls cell fate; 2) Understanding how the function of epigenetic regulators in stem cell control differ between pluripotent embryonic stem cells and unipotent skin stem cells; and 3) Elucidating how changes in the functions of epigenetic regulators lead to diseases and cancer.

 

Polycomb complex in stem cell control

Polycomb group proteins are evolutionarily conserved chromatin modifiers well known for their repressive function. Polycomb complexes exist as two multi-subunit complexes, Polycomb repressive complex (PRC) 1 and PRC2. PRC1 and PRC2 regulate gene expression by catalyzing histone tails modification. PRC2 trimethylates histone H3 on lysine 27 (H3K27me3) and PRC1 attaches a ubiquitin unit to lysine 119 of histone H2A (H2AK119ub). Modification of the histones by both complexes promotes chromatin compaction and gene silencing (Figure 2). These complexes are critical for body patterning and stem cell function during development.  

 

 

 

 

 

 

 

 

 

 

 

Basal layer (EpSCs)

Suprabasal layers (differentiated cells)

Figure 1. The skin structure and appendages (see text for details).

Dermis

Epidermis

Polycomb new2.png

Figure 2. Gene repression by Polycomb complexes (see text for details).