Single-cell transcriptome atlas of male mouse pituitary across postnatal life highlighting its stem cell landscape

By: Silke De Vriendt, Emma Laporte, Berkehür Abaylı, Julie Hoekx, Florian Hermans,

Diether Lambrechts, and Hugo Vankelecom

The pituitary gland, referred to as the ‘master endocrine gland’, is a small but crucial part of our hormonal system. Located at the base of the brain, it plays a vital role in regulating various body physiological functions by producing several hormones that, among others, control growth, metabolism and reproduction. Studying the pituitary gland is essential because it helps us understand how these critical processes are regulated and what happens in diseased or perturbed conditions.

Before, we have discovered that the pituitary gland contains a population of stem cells. These pituitary stem cells are marked by the expression of SOX2. By studying these stem cells, scientists gain insights into how the pituitary gland maintains its function in homeostatic and challenged conditions throughout the lifetime. However, the cellular complexity of the pituitary stem cell compartment remains poorly charted.

In our research, we used single-cell transcriptomics to decipher the cellular and molecular landscape of the mouse pituitary and its stem cells across postnatal life. First, we better characterized the different stem cell populations, revealing roles for new regulatory factors and pathways in pituitary stem cell regulation (such as Krüppel-like transcription factor 5 (KLF5) and epidermal growth factor (EGF)). Additionally, we bioinformatically explored how pituitary stem cells interact with other cell types within the gland. To validate the predicted interactions, we used our in-house developed pituitary stem cell-derived organoid model. Organoids grow from tissue stem cells, allowing us to study stem cell behavior in an accessible and controllable in vitro environment.

The computational power and support provided by VSC were highly instrumental in analyzing the data generated in this study.

Next, we analyzed how pituitary stem cell characteristics change at different key postnatal ages. One of the significant findings was the occurrence of an increased inflammatory phenotype in old pituitary and its stem cells, aligning with the general concept of ‘inflammaging’ (i.e. gradually increasing tissue inflammation at aging). Finally, we showed the translatability of the mouse atlas-based findings to human pituitary, particularly regarding aging-associated expression profiles.

Our research enhances our understanding of how the pituitary gland functions and ages which is very important because of its key role in the body. The computational power and support provided by VSC were highly instrumental in analyzing the data generated in this study. We are excited about the potential for further insights in this area as well as the translation into clinical settings.

Read the full article in ScienceDirect here