Single-cell transcriptome atlas of male mouse pituitary across postnatal life highlighting its stem cell landscape
Description
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 Krüppel-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.
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Steps to reproduce
Mouse pituitary single-cell RNA-sequencing (scRNA-seq) datasets of all ages (neonatal (E-MTAB-11337), young-adult (E-MTAB- 10021), middle-aged (E-MTAB- 10021) and old (E-MTAB-14067) in both healthy (undamaged) and damaged condition were integrated following the Seurat (v4.2.0) integration workflow. The scRNA-seq datasets of the pituitary organoids from the different ages (E-MTAB-14008) were integrated and projected onto the pituitary atlas using Seurat’s MapQuery function. Both loom files and annotated Seurat objects were established for interactive exploration of the comprehensive pituitary atlas (all ages; (un)damaged condition) and organoid dataset (all ages). Loom files were made with Loompy v2.0.17 (Linnarsson lab, www.loompy.org) and can be uploaded into SCope (available from Aerts lab, https://scope.aertslab.org).