Lei Pin-Ji, Ruscic Katarina J, Roh Kangsan, Rajotte Johanna J, O'Melia Meghan J, Bouta Echoe M, Marquez Marla, Pereira Ethel R, Kumar Ashwin S, Arroyo-Ataz Guillermo, Razavi Mohammad S, Zhou Hengbo, Menzel Lutz, Kumra Heena, Duquette Mark, Huang Peigen, Baish James W, Munn Lance L, Ubellacker Jessalyn M, Jones Dennis, Padera Timothy P
bioRxiv. 2023 Nov 19:2023.11.18.567621. doi: 10.1101/2023.11.18.567621.
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 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 collecting lymphatic vessels in mouse dermis at various ages. We identified genes that distinguish LMCs from other types of muscle cells, characterized the phenotypical and transcriptomic changes in LMCs in aged vessels, and uncovered a pro-inflammatory microenvironment that suppresses the contractile apparatus in advanced-aged LMCs. Our findings provide a valuable resource to accelerate future research for the identification of potential drug targets on LMCs to preserve lymphatic vessel function as well as supporting studies to identify genetic causes of primary lymphedema currently with unknown molecular explanation.
集合淋巴管壁内的淋巴管平滑肌细胞（LMCs）呈现出强直性和自主性的阶段性收缩，这些收缩驱动活跃的淋巴运输，以维持组织液稳态并支持免疫监视。LMCs受损会破坏淋巴功能，并与多种疾病相关。尽管它们很重要，但在很大程度上仍缺乏对LMCs转录特征及其在正常和疾病背景下与淋巴功能关系的了解。我们已经生成了一个全面的转录单细胞图谱，包括不同年龄小鼠真皮中集合淋巴管的LMCs。我们鉴定了区分LMCs与其他类型肌肉细胞的基因，表征了老年血管中LMCs的表型和转录组变化，并发现了一种促炎微环境，该微环境会抑制老年LMCs中的收缩装置。我们的研究结果提供了宝贵的资源，可加速未来关于识别LMCs上潜在药物靶点以维持淋巴管功能的研究，同时支持目前对原发性淋巴水肿分子解释未知的遗传病因识别研究。
