Aging-induced changes in lymphatic muscle cell transcriptomes are associated with reduced pumping of peripheral collecting lymphatic vessels in mice

IF 10.7 1区生物学 Q1 CELL BIOLOGY

Developmental cell Pub Date : 2024-12-27 DOI:10.1016/j.devcel.2024.12.010

Pin-Ji Lei, Katarina J. Ruscic, Kangsan Roh, Johanna J. Rajotte, Meghan J. O’Melia, Echoe M. Bouta, Marla Marquez, Ethel R. Pereira, Ashwin S. Kumar, Mohammad S. Razavi, Hengbo Zhou, Lutz Menzel, Liqing Huang, Heena Kumra, Mark Duquette, Peigen Huang, James W. Baish, Lance L. Munn, Natasza A. Kurpios, Jessalyn M. Ubellacker, Timothy P. Padera

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Abstract

Lymphatic muscle cells (LMCs) within the wall of collecting lymphatic vessels exhibit tonic and autonomous phasic contractions, which drive active lymph transport to maintain tissue-fluid homeostasis and support immune surveillance. Damage to LMCs disrupts lymphatic function and is related to various diseases. Despite their importance, knowledge of the gene transcriptional signatures in LMCs and how they relate to lymphatic function in normal and disease contexts is largely missing. We have generated a comprehensive transcriptional single-cell atlas—including LMCs—of peripheral collecting lymphatic vessels from mice across the lifespan. We identified genes that distinguish LMCs from other types of muscle cells, characterized the phenotypical and transcriptomic changes in LMCs in aged vessels, and identified a proinflammatory microenvironment that suppresses the contractile apparatus in LMCs from advanced-aged mice. Our findings provide a valuable resource to accelerate future research for the identification of potential drug targets on LMCs to improve lymphatic vessel function.

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衰老诱导的淋巴肌肉细胞转录组的变化与小鼠外周血集淋巴管泵送减少有关

收集淋巴管壁内的淋巴肌细胞（LMCs）表现出强直和自主的阶段性收缩，从而驱动活跃的淋巴运输以维持组织-液体稳态并支持免疫监视。淋巴细胞损伤会破坏淋巴功能，并与多种疾病有关。尽管它们很重要，但关于lmc中的基因转录特征以及它们在正常和疾病情况下与淋巴功能的关系的知识在很大程度上是缺失的。我们已经生成了一个全面的转录单细胞图谱，包括小鼠整个生命周期的外周血淋巴血管的lmc。我们鉴定了将lmc与其他类型肌肉细胞区分开来的基因，表征了衰老血管中lmc的表型和转录组变化，并鉴定了抑制老年小鼠lmc中收缩装置的促炎微环境。我们的发现为加快未来的研究提供了宝贵的资源，以确定lmc的潜在药物靶点，以改善淋巴管功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Developmental cell 生物-发育生物学

CiteScore

18.90

自引率

1.70%

发文量

203

审稿时长

3-6 weeks

期刊介绍： Developmental Cell, established in 2001, is a comprehensive journal that explores a wide range of topics in cell and developmental biology. Our publication encompasses work across various disciplines within biology, with a particular emphasis on investigating the intersections between cell biology, developmental biology, and other related fields. Our primary objective is to present research conducted through a cell biological perspective, addressing the essential mechanisms governing cell function, cellular interactions, and responses to the environment. Moreover, we focus on understanding the collective behavior of cells, culminating in the formation of tissues, organs, and whole organisms, while also investigating the consequences of any malfunctions in these intricate processes.