Tang XinYu, Wang Yan, Xu RuiRong
Doctoral student of Grade 2024, First Clinical Medical College of, Shandong University of Traditional Chinese Medicine, Jinan, China.
Department of Hematology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Stem Cell Res Ther. 2025 May 1;16(1):214. doi: 10.1186/s13287-025-04350-1.
Hematopoietic stem cells (HSCs) are the primitive cells that give rise to common precursors for all blood cell lineages. Abnormalities in their number and/or function are important factors leading to the decline of immune function and the occurrence of various systemic diseases. Phase separation refers to a physicochemical mechanism in which intracellular liquid-liquid phase separation (LLPS) forms membrane-less organelles. It participates in various physiological activities and is related to the occurrence of diseases. Studies have shown that the functional activity of HSCs is regulated by complex mechanisms, and phase separation is closely related to these complex mechanisms such as genetic regulation, epigenetic regulation, microenvironment regulation, gene expression, autophagy degradation, and cell proliferation. With the deepening of research, the importance of phase separation in the pathogenesis and treatment of diseases such as leukemia and tumors has gradually emerged, but the deep mechanism of its regulation of HSCs genetic regulation still lacks exploration, and the direction of clinical targeted therapy is not yet clear. Here, we will summarize and elaborate the genetic regulation mechanism of HSCs, discuss the relationship between phase separation and the functional regulation of HSCs, and analyze the possibility of phase separation participating in the genetic regulation of HSCs to treat diseases, in order to provide help for the clinical implementation of targeted therapy for HSCs regulation.
造血干细胞（HSCs）是产生所有血细胞谱系共同前体的原始细胞。其数量和/或功能异常是导致免疫功能下降和各种全身性疾病发生的重要因素。相分离是细胞内液-液相分离（LLPS）形成无膜细胞器的一种物理化学机制。它参与各种生理活动，并与疾病的发生有关。研究表明，造血干细胞的功能活性受复杂机制调控，相分离与遗传调控、表观遗传调控、微环境调控、基因表达、自噬降解和细胞增殖等这些复杂机制密切相关。随着研究的深入，相分离在白血病和肿瘤等疾病的发病机制及治疗中的重要性逐渐显现，但相分离调控造血干细胞遗传调控的深层机制仍缺乏探索，临床靶向治疗方向尚不明确。在此，我们将总结并阐述造血干细胞的遗传调控机制，探讨相分离与造血干细胞功能调控之间的关系，并分析相分离参与造血干细胞遗传调控治疗疾病的可能性，旨在为造血干细胞调控靶向治疗的临床实施提供帮助。
