Department of Stem Cell and Regenerative Biotechnology and Institute of Advanced Regenerative Science, Konkuk University, Seoul 05029, Korea.
Cells. 2022 May 19;11(10):1692. doi: 10.3390/cells11101692.
The lymphatic system is critical for maintaining the homeostasis of lipids and interstitial fluid and regulating the immune cell development and functions. Developmental anomaly-induced lymphatic dysfunction is associated with various pathological conditions, including lymphedema, inflammation, and cancer. Most lymphatic endothelial cells (LECs) are derived from a subset of endothelial cells in the cardinal vein. However, recent studies have reported that the developmental origin of LECs is heterogeneous. Multiple regulatory mechanisms, including those mediated by signaling pathways, transcription factors, and epigenetic pathways, are involved in lymphatic development and functions. Recent studies have demonstrated that the epigenetic regulation of transcription is critical for embryonic LEC development and functions. In addition to the chromatin structures, epigenetic modifications may modulate transcriptional signatures during the development or differentiation of LECs. Therefore, the understanding of the epigenetic mechanisms involved in the development and function of the lymphatic system can aid in the management of various congenital or acquired lymphatic disorders. Future studies must determine the role of other epigenetic factors and changes in mammalian lymphatic development and function. Here, the recent findings on key factors involved in the development of the lymphatic system and their epigenetic regulation, LEC origins from different organs, and lymphatic diseases are reviewed.
淋巴系统对于维持脂质和细胞间质液的内环境稳定，以及调节免疫细胞的发育和功能至关重要。发育异常引起的淋巴功能障碍与多种病理状况有关，包括淋巴水肿、炎症和癌症。大多数淋巴管内皮细胞（LEC）来源于心静脉中的一组内皮细胞。然而，最近的研究报告称，LEC 的发育起源具有异质性。多种调节机制，包括信号通路、转录因子和表观遗传途径介导的调节机制，参与了淋巴管的发育和功能。最近的研究表明，转录的表观遗传调控对于胚胎 LEC 的发育和功能至关重要。除了染色质结构外，表观遗传修饰可能在 LEC 的发育或分化过程中调节转录特征。因此，了解参与淋巴管系统发育和功能的表观遗传机制有助于管理各种先天性或获得性的淋巴系统疾病。未来的研究必须确定其他表观遗传因素以及哺乳动物淋巴管发育和功能中的变化的作用。本文综述了淋巴管系统发育中的关键因素及其表观遗传调控、来自不同器官的 LEC 起源，以及淋巴疾病的最新发现。
