Changes in gene expression in sebaceous glands have now been mapped out in detail. This research illustrates the shifts in gene activity that occur during the process of sebum production and points to new potential factors that could influence sebum output.
For the first time, a collaborative effort between the Faculty of Veterinary Medicine and the Interdisciplinary Centre for Bioinformatics (IZBI) at Leipzig University has achieved a detailed spatial mapping of gene expression changes in sebaceous glands. This study captures high-resolution variations in gene activity throughout the sebum synthesis process and unveils new candidates that could regulate sebum production. These findings have been published in the Journal of Biological Chemistry.
Sebaceous glands play a crucial role in keeping the skin’s structure and function intact. During a process known as holocrine secretion, peripheral cells within the gland accumulate a large quantity of lipids, then move towards the gland’s center and burst, releasing an oily substance (sebum) that helps protect and moisturize the skin. In humans and most mammals, sebum also has other significant but not yet fully understood roles, such as shielding against UVB-related cell death or aiding the skin’s immune response. Additionally, sebum production can influence energy metabolism throughout the body. Any disruption in the sebaceous glands is a major contributor to acne and can also be involved in other dermatological conditions like eczema and psoriasis. Recent findings indicate that sebum production may have essential effects on the immune system and impact overall energy metabolism. Hence, regulating sebum secretion could be a promising therapeutic approach for not just skin ailments, but also for infectious and metabolic illnesses.
“Apart from their role in skin health, sebaceous glands serve as an interesting and accessible model for exploring fundamental biological mechanisms such as lipid production, stem cell functionality, or tumor development,” states Professor Marlon R. Schneider. He leads the Institute of Veterinary Physiology at Leipzig University and was the driving force behind the study.
Despite their significance, a comprehensive study on the gene expression changes occurring in sebocytes (the cells of the sebaceous gland) responsible for sebum production was lacking. The recently published research integrates novel techniques such as spatial gene expression analysis, pseudotime analysis, and functional enrichment to track the developmental progression of sebaceous gland cells leading to cell lysis. Utilizing four distinct differentiation stages identified through unsupervised clustering, the data reveal a sequential modulation of cellular functions linked to specific gene sets, covering cell proliferation, oxidative phosphorylation, lipid generation, and cell death. These findings were validated against existing sebaceous gland transcriptome data and backed by protein expression pattern analyses of selected transcripts from the Human Protein Atlas. An online tool that is openly accessible and searchable also complements this study.
PD Dr. Hans Binder, a former director of the Interdisciplinary Centre for Bioinformatics (IZBI) at Leipzig University, highlights the relevance of the online bioinformatics tool developed in tandem: “The method is extremely data-driven, enabling researchers globally to search and independently analyze our data.”
By combining various methodologies, the research offers a fresh and thorough understanding of the gene expression changes involved in sebaceous gland differentiation. The data implies a continuous evolution of sebaceous cells through a progressive modulation of cellular functions associated with specific gene sets, revealing new players in sebum production and paving the way for future therapeutic interventions of medical importance.
Next Objective: Skin Disorders and Tear Production
Next, the research will delve deeper into the gene expression shifts within sebaceous glands related to various skin conditions, particularly eczema and psoriasis, as well as sebaceous gland tumors. These studies will utilize advancements in spatial transcriptome analysis, which permits results to be captured at the single-cell level.
Dr. Maria Schmidt, the primary author of the study, emphasizes the innovative nature of this technique: “In 2020, the esteemed journal Nature recognized spatially resolved gene expression as its Method of the Year. Merging molecular biology with microscopy, this highly data-driven approach, coupled with advanced bioinformatics, provides novel insights into the spatial and temporal organization of biological processes at the cellular level.”
Beyond skin sebaceous glands, there are also specialized sebaceous glands in the body that carry out specific functions. For example, the Meibomian glands located along the eyelid margins secrete oils that contribute to the lipid layer of tears, preventing evaporation. Disruption of this lipid barrier leads to inflammation and dry eye symptoms. A similar analysis of gene expression changes in the meibomian glands is also approaching completion.
