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

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES iScience Pub Date : 2025-02-21 Epub Date: 2025-01-06 DOI:10.1016/j.isci.2024.111708

Silke De Vriendt , Emma Laporte , Berkehür Abaylı , Julie Hoekx , Florian Hermans , Diether Lambrechts , Hugo Vankelecom

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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 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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雄性小鼠出生后垂体单细胞转录组图谱显示其干细胞景观。

脑下垂体是控制内分泌系统的主要腺体。我们结合现有的和新的数据，构建了雄性小鼠内分泌垂体单细胞转录组图谱，涵盖了健康和损伤状态下重要的出生后年龄。我们通过关注其干细胞并研究其复杂的身份（揭示干细胞标记物）和利基（精确定位调节因子），证明了这种新的图谱在解开垂体（病理）生物学方面的强大适用性。重要的是，我们利用垂体干细胞类器官从功能上验证了转录组学研究结果，揭示了kr ppel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）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力学的变化，增强了老年垂体和干细胞的炎症/免疫性质。最后，我们展示了基于小鼠地图集的发现对人类的可翻译性，特别是关于衰老相关的概况。这张垂体sc图是解开垂体（病理）生物学的一个有价值的工具。

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

期刊介绍： Science has many big remaining questions. To address them, we will need to work collaboratively and across disciplines. The goal of iScience is to help fuel that type of interdisciplinary thinking. iScience is a new open-access journal from Cell Press that provides a platform for original research in the life, physical, and earth sciences. The primary criterion for publication in iScience is a significant contribution to a relevant field combined with robust results and underlying methodology. The advances appearing in iScience include both fundamental and applied investigations across this interdisciplinary range of topic areas. To support transparency in scientific investigation, we are happy to consider replication studies and papers that describe negative results. We know you want your work to be published quickly and to be widely visible within your community and beyond. With the strong international reputation of Cell Press behind it, publication in iScience will help your work garner the attention and recognition it merits. Like all Cell Press journals, iScience prioritizes rapid publication. Our editorial team pays special attention to high-quality author service and to efficient, clear-cut decisions based on the information available within the manuscript. iScience taps into the expertise across Cell Press journals and selected partners to inform our editorial decisions and help publish your science in a timely and seamless way.