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Project

Unraveling the pituitary stem cells’ biology in the injured, regenerating, and aging gland

The pituitary is the master regulator of our hormonal system. Injury and aging are key threats to its vital role in governing body physiology. We discovered that the (mouse) pituitary can regenerate its cells after local injury, a competence however quickly vanishing at aging. Here, we will in-depth decipher the mechanisms underlying pituitary stem cell activation and ensuing regeneration, and why this fails with aging. By applying single-cell (sc) transcriptomics and in vitro (stem-cell organoid) and in vivo scrutiny, we identified interleukin-6 (IL-6) to be promptly upregulated in the pituitary upon damage and to activate the stem cells. Here, we will disentangle the involvement of two other important cytokines highly expressed in the damaged gland, i.e. IL-11 and IL-22, together with their common downstream JAK/STAT signaling pathway. Intriguingly, the failing stem-cell activation response in the aging pituitary concurs with an elevated inflammatory state. Here, we will deeply untangle this ‘inflammaging’ phenotype while anti-inflammatory treatments will be examined for reviving pituitary stem cell functionality. Finally, we will translate our mouse-based findings to human pituitary through sc transcriptomics and organoid tactics. Our study will strongly advance our understanding of pituitary repair after injury and its failure at aging, thus opening translational perspectives to treat pituitary defects, as well as to decelerate pituitary aging or rejuvenate the old gland.

Date:1 Mar 2023 →  Today
Keywords:Pituitary aging, Pituitary stem cells, Pituitary regeneration
Disciplines:Endocrinology, Stem cell biology, Organ physiology, Pathophysiology, Regenerative medicine not elsewhere classified
Project type:PhD project