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禁食诱导代谢转换以及脂类处理和神经元相互作用在室管膜细胞中的空间再分布。

Fasting induces metabolic switches and spatial redistributions of lipid processing and neuronal interactions in tanycytes.

机构信息

Service of Endocrinology, Diabetology, and Metabolism, Lausanne University Hospital, Lausanne, Switzerland.

Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.

出版信息

Nat Commun. 2024 Aug 4;15(1):6604. doi: 10.1038/s41467-024-50913-w.

DOI:10.1038/s41467-024-50913-w
PMID:39098920
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11298547/
Abstract

The ependyma lining the third ventricle (3V) in the mediobasal hypothalamus plays a crucial role in energy balance and glucose homeostasis. It is characterized by a high functional heterogeneity and plasticity, but the underlying molecular mechanisms governing its features are not fully understood. Here, 5481 hypothalamic ependymocytes were cataloged using FACS-assisted scRNAseq from fed, 12h-fasted, and 24h-fasted adult male mice. With standard clustering analysis, typical ependymal cells and β2-tanycytes appear sharply defined, but other subpopulations, β1- and α-tanycytes, display fuzzy boundaries with few or no specific markers. Pseudospatial approaches, based on the 3V neuroanatomical distribution, enable the identification of specific versus shared tanycyte markers and subgroup-specific versus general tanycyte functions. We show that fasting dynamically shifts gene expression patterns along the 3V, leading to a spatial redistribution of cell type-specific responses. Altogether, we show that changes in energy status induce metabolic and functional switches in tanycyte subpopulations, providing insights into molecular and functional diversity and plasticity within the tanycyte population.

摘要

第三脑室(3V)中脑基底部的室管膜细胞在能量平衡和葡萄糖稳态中起着至关重要的作用。它具有高度的功能异质性和可塑性,但控制其特征的潜在分子机制尚不完全清楚。在这里,我们使用 FACS 辅助 scRNAseq 从进食、12 小时禁食和 24 小时禁食的成年雄性小鼠中对 5481 个下丘脑室管膜细胞进行了分类。通过标准聚类分析,典型的室管膜细胞和β2-室管膜细胞显示出明显的边界,但其他亚群,β1-和α-室管膜细胞,与很少或没有特定标记的模糊边界。基于 3V 神经解剖分布的伪空间方法,能够识别特定的和共享的室管膜细胞标记物以及亚群特异性的和一般的室管膜细胞功能。我们表明,禁食会沿 3V 动态地改变基因表达模式,导致细胞类型特异性反应的空间再分布。总的来说,我们表明能量状态的变化会在室管膜细胞亚群中诱导代谢和功能转换,为室管膜细胞群体中的分子和功能多样性和可塑性提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/2320e19d53e5/41467_2024_50913_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/0dd09668f0a2/41467_2024_50913_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/de0f3bd01169/41467_2024_50913_Fig2_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/e142f69755eb/41467_2024_50913_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/dc5c3b883767/41467_2024_50913_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/bf542d543b41/41467_2024_50913_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/2320e19d53e5/41467_2024_50913_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/0dd09668f0a2/41467_2024_50913_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/de0f3bd01169/41467_2024_50913_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/b4d2853d3e6f/41467_2024_50913_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/e142f69755eb/41467_2024_50913_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/dc5c3b883767/41467_2024_50913_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/bf542d543b41/41467_2024_50913_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b77/11298547/2320e19d53e5/41467_2024_50913_Fig7_HTML.jpg

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