De Vriendt Silke, Laporte Emma, Abaylı Berkehür, Hoekx Julie, Hermans Florian, Lambrechts Diether, Vankelecom Hugo
Laboratory of Tissue Plasticity in Health and Disease, Cluster of Stem Cell and Developmental Biology, Department of Development and Regeneration, KU Leuven, 3000 Leuven, Belgium.
Department of Cardiology and Organ Systems (COS), Biomedical Research Institute (BIOMED), Faculty of Medicine and Life Sciences, Hasselt University, 3590 Diepenbeek, Belgium.
iScience. 2025 Jan 6;28(2):111708. doi: 10.1016/j.isci.2024.111708. eCollection 2025 Feb 21.
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.
垂体是调控内分泌系统的主要腺体。我们通过整合现有数据和新数据，构建了雄性小鼠内分泌垂体的单细胞转录组图谱，涵盖了健康和损伤状态下重要的出生后年龄段。我们通过聚焦垂体干细胞并研究其复杂特性（揭示干细胞标志物）和微环境（确定调控因子），证明了这个新图谱在揭示垂体（病理）生物学方面具有很强的适用性。重要的是，我们使用垂体干细胞类器官对转录组学研究结果进行了功能验证，揭示了Krüppel样转录因子5（KLF5）、激活蛋白-1（AP-1）复合物和表皮生长因子（EGF）信号通路在垂体干细胞调控中的作用。我们的研究证实了衰老过程中干细胞动态的变化，强化了老年垂体和干细胞中的炎症/免疫特性。最后，我们展示了基于小鼠图谱的研究结果可转化至人类，特别是在与衰老相关的特征方面。这个垂体单细胞图谱是揭示垂体（病理）生物学的宝贵工具。
