Yamashita Masayuki
Division of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo.
Rinsho Ketsueki. 2022;63(8):918-927. doi: 10.11406/rinketsu.63.918.
Hematopoietic stem cells (HSCs) are tissue-specific stem cells that are critical for homeostasis and regeneration of the hematopoietic system. Multiple mechanisms exist that help maintain the size and integrity of the HSC pool after exposure to various insults to provide all lineages of blood cells throughout life. Clonal hematopoiesis, an age-related clonal mosaicism detected in the hematopoietic system and governed by aberrant HSC clones with somatic mutations, has recently been identified as an important risk factor for hematological malignancy and cardiovascular disease. Cells with a somatic mutation can present neoantigens via the major histocompatibility complex and can be recognized and eliminated by antigen-specific T cells. However, whether this mechanism also acts to maintain HSC pool integrity remains largely unclear. In this review, I have summarized mechanisms known to support the lifelong maintenance of HSC numbers and function, introduced recent findings that indicate active interaction between HSCs and T cells, and discussed potential effects of its dysregulation on hematological diseases.
造血干细胞(HSCs)是组织特异性干细胞,对造血系统的稳态和再生至关重要。存在多种机制,有助于在暴露于各种损伤后维持造血干细胞库的大小和完整性,从而在整个生命过程中提供所有血细胞谱系。克隆性造血是在造血系统中检测到的一种与年龄相关的克隆镶嵌现象,由具有体细胞突变的异常造血干细胞克隆所控制,最近已被确定为血液系统恶性肿瘤和心血管疾病的重要危险因素。具有体细胞突变的细胞可通过主要组织相容性复合体呈递新抗原,并可被抗原特异性T细胞识别和清除。然而,这种机制是否也有助于维持造血干细胞库的完整性在很大程度上仍不清楚。在这篇综述中,我总结了已知的支持造血干细胞数量和功能终身维持的机制,介绍了表明造血干细胞与T细胞之间存在活跃相互作用的最新发现,并讨论了其失调对血液系统疾病的潜在影响。