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

Abstract

The pituitary represents the master gland governing the endocrine system. We constructed a single-cell (sc) transcriptomic atlas of male mouse endocrine pituitary by incorporating existing and new data, spanning important postnatal ages in both healthy and injured condition. We demonstrate strong applicability of this new atlas to unravel pituitary (patho)biology by focusing on its stem cells and investigating their complex identity (unveiling stem cell markers) and niche (pinpointing regulatory factors). Importantly, we functionally validated transcriptomic findings using pituitary stem cell organoids, revealing roles for Kru<euro>ppel-like transcription factor 5 (KLF5), activator protein-1 (AP-1) complex and epidermal growth factor (EGF) pathways in pituitary stem cell regulation. Our investigation substantiated changes in stem cell dynamics during aging, reinforcing the inflammatory/immune nature in elderly pituitary and stem cells. Finally, we show translatability of mouse atlas-based findings to humans, particularly regarding aging-associated profile. This pituitary sc map is a valuable tool to unravel pituitary (patho)biology.