New Method Enables Molecular Portrait of Sebum Production

Leipzig scientists unlock the genetic secrets of sebaceous glands for the first time

In a collaborative project between the University of Leipzig's Faculty of Veterinary Medicine and its Interdisciplinary Center for Bioinformatics, researchers have, for the first time, spatially mapped changes in gene expression within sebaceous glands. The study, published in the prestigious Journal of Biological Chemistry, provides high-resolution documentation of gene expression shifts during sebum synthesis and identifies new candidates for modulating sebum production.

Sebaceous glands are essential for maintaining the structure and function of the skin. Through a process called holocrine secretion, cells at the gland's periphery accumulate vast quantities of lipid molecules, migrate toward the center, and ultimately rupture, releasing an oily secretion (sebum) that protects and moisturizes the skin's surface. In humans and most mammals, sebum also plays other critical—but largely unexplored—roles, such as shielding against UVB-induced apoptosis (cell death) and contributing to the skin's innate immune response. Sebum production can even influence whole-body energy metabolism. Dysregulation of sebaceous glands is a key factor in acne development and also plays a role in other skin conditions, including atopic dermatitis—a chronic, itchy inflammation of the upper skin layers—and psoriasis, also known as plaque psoriasis. Recent studies further suggest that sebum production may have significant immunomodulatory effects and could impact the organism's overall metabolic balance. As such, modulating sebum secretion may offer an attractive therapeutic target not only for skin diseases but also for infectious and metabolic disorders.

"Beyond their importance for skin health, sebaceous glands provide an accessible and compelling model for studying fundamental biological processes, such as lipid synthesis, stem cell function, and tumor development," explains Professor Dr. Marlon R. Schneider, who heads the Institute of Veterinary Physiology at the University of Leipzig and initiated and supervised the study.

However, the shifts in gene expression within sebocytes (sebaceous gland cells) that drive sebum production had never been examined in detail—until now. In this newly published study, the two research teams integrated cutting-edge methods, including spatial gene expression analysis, pseudotime trajectory modeling, and functional enrichment, to map the progressive development of sebaceous gland cells up to their eventual disintegration. Based on four stages of cell differentiation identified through unsupervised clustering, the data reveal a sequential modulation of cellular functions associated with distinct gene sets—ranging from cell proliferation and oxidative phosphorylation to lipid synthesis and, finally, cell death. The findings were validated by comparing them with previously published sebaceous gland transcriptome data and further supported by analyzing protein expression patterns of selected transcripts in the publicly available Human Protein Atlas. The study is also complemented by a freely accessible, searchable online tool.

Dr. Hans Binder, former managing director of the University of Leipzig's Interdisciplinary Center for Bioinformatics (IZBI), emphasizes the significance of a parallel-developed bioinformatics tool: "This approach is highly data-driven. With this tool, researchers worldwide can explore and independently analyze our datasets."

By combining multiple methods, the study provides a comprehensive and novel understanding of the gene expression dynamics underlying sebaceous gland differentiation. The data suggest a continuous progression of sebaceous cells through sequential modulation of cellular functions, each linked to specific gene sets. The research identifies new players in sebum production, offering fresh avenues for modulating sebum levels and highlighting future experimental approaches with potential medical relevance.

Next Target: Skin Diseases and Tears

The next step will involve a closer examination of gene expression changes in the sebaceous gland in connection with specific skin diseases, particularly atopic dermatitis and psoriasis, as well as sebaceous gland tumors. For these investigations, researchers will employ the next developmental stage of spatial transcriptomics—a method capable of delivering single-cell resolution. Dr. Maria Schmidt, the study's lead author, explains the significance of the approach: "Spatially resolved gene expression was named 'Method of the Year' in 2020 by the prestigious scientific journal Nature. Combining molecular biology and microscopy, it is a highly data-driven technique that, when paired with advanced bioinformatics, provides unprecedented insights into the spatial and temporal organization of life processes at cellular resolution."

Beyond the sebaceous glands of the skin, specialized sebaceous glands perform distinct functions in the body. For example, the meibomian glands along the eyelid margins produce an oily fluid that forms the lipid layer of the tear film. This layer prevents tear evaporation, and when disrupted, it can lead to inflammation and dry eye syndrome. A similar mapping of gene expression changes in the meibomian gland by the research team is nearing completion.

Scientific Contacts:

• Dr. Maria Schmidt Interdisciplinary Center for Bioinformatics (IZBI) Phone: +49 341 97-16670 Email: [email protected] Web: https://www.izbi.uni-leipzig.de/
• Prof. Dr. Marlon Schneider Institute of Veterinary Physiology Faculty of Veterinary Medicine Phone: +49 341 97-38061 Email: [email protected]

Original Publication:

"A spatial portrait of the human sebaceous gland transcriptional program"Journal of Biological Chemistry DOI: 10.1016/j.jbc.2024.107442

University of Leipzig