Center for Stem Cell and Regenerative Medicine and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Liangzhu Laboratory, Zhejiang University, Hangzhou, China.
Adv Exp Med Biol. 2023;1442:29-44. doi: 10.1007/978-981-99-7471-9_3.
Hematopoietic stem cells (HSCs) are adult stem cells with the ability of self-renewal and multilineage differentiation into functional blood cells, thus playing important roles in the homeostasis of hematopoiesis and the immune response. Continuous self-renewal of HSCs offers fresh supplies for the HSC pool, which differentiate into all kinds of mature blood cells, supporting the normal functioning of the entire blood system. Nevertheless, dysregulation of the homeostasis of hematopoiesis is often the cause of many blood diseases. Excessive self-renewal of HSCs leads to hematopoietic malignancies (e.g., leukemia), while deficiency in HSC regeneration results in pancytopenia (e.g., anemia). The regulation of hematopoietic homeostasis is finely tuned, and the rapid development of high-throughput sequencing technologies has greatly boosted research in this field. In this chapter, we will summarize the recent understanding of epigenetic regulators including DNA methylation, histone modification, chromosome remodeling, noncoding RNAs, and RNA modification that are involved in hematopoietic homeostasis, which provides fundamental basis for the development of therapeutic strategies against hematopoietic diseases.
造血干细胞（HSCs）是具有自我更新和多能性分化为功能性血细胞能力的成体干细胞，因此在造血和免疫反应的稳态中发挥重要作用。HSCs 的持续自我更新为 HSC 池提供了新鲜的供应，HSC 池分化为各种成熟的血细胞，支持整个血液系统的正常功能。然而，造血稳态的失调常常是许多血液疾病的原因。HSCs 的过度自我更新导致造血恶性肿瘤（例如白血病），而 HSC 再生的缺陷则导致全血细胞减少症（例如贫血）。造血稳态的调节非常精细，高通量测序技术的快速发展极大地推动了该领域的研究。在本章中，我们将总结参与造血稳态的表观遗传调节剂（包括 DNA 甲基化、组蛋白修饰、染色质重塑、非编码 RNA 和 RNA 修饰）的最新认识，这为开发针对造血疾病的治疗策略提供了基础。
