Vasiloudis Ninos Ioannis, Paschoudi Kiriaki, Beta Christina, Georgolopoulos Grigorios, Psatha Nikoletta
Department of Genetics, Development and Molecular Biology, School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.
Gene and Cell Therapy Center, Hematology Clinic-Bone Marrow Transplantation Unit, "George Papanikolaou" Hospital, 57010 Thessaloniki, Greece.
Int J Mol Sci. 2025 Jun 30;26(13):6342. doi: 10.3390/ijms26136342.
Erythropoiesis, the process driving the differentiation of hematopoietic stem and progenitor cells to mature erythrocytes, unfolds through tightly orchestrated developmental stages, each defined by profound epigenetic remodeling. From the initial commitment of hematopoietic progenitors to the terminal enucleation of erythrocytes, dynamic changes in chromatin accessibility, transcription factor occupancy, and three-dimensional genome architecture govern lineage specification and stage-specific gene expression. Advances in our understanding of the regulatory genome have uncovered how non-coding elements, including enhancers, silencers, and insulators, shape the transcriptional landscape of erythroid cells. These elements work in concert with lineage-determining transcription factors to establish and maintain erythroid identity. Disruption of these epigenetic programs-whether by inherited mutations, somatic alterations, or environmental stress-can lead to a wide range of hematologic disorders. Importantly, this growing knowledge base has opened new therapeutic avenues, enabling the development of precision tools that target regulatory circuits to correct gene expression. These include epigenetic drugs, enhancer-targeted genome editing, and lineage-restricted gene therapies that leverage endogenous regulatory logic. As our understanding of erythroid epigenomics deepens, so too does our ability to design rational, cell-type-specific interventions for red blood cell disorders.
红细胞生成是一个促使造血干细胞和祖细胞分化为成熟红细胞的过程，它通过精心编排的发育阶段逐步展开，每个阶段都由深刻的表观遗传重塑所定义。从造血祖细胞的初始定向分化到红细胞的终末去核，染色质可及性、转录因子占据情况以及三维基因组结构的动态变化控制着细胞谱系的特化和阶段特异性基因表达。我们对调控基因组理解的进展揭示了包括增强子、沉默子和绝缘子在内的非编码元件如何塑造红系细胞的转录格局。这些元件与决定细胞谱系的转录因子协同作用，以建立和维持红系细胞特性。这些表观遗传程序的破坏——无论是通过遗传突变、体细胞改变还是环境应激——都可能导致多种血液系统疾病。重要的是，这一不断增长的知识库开辟了新的治疗途径，使得能够开发针对调控回路以纠正基因表达的精准工具。这些工具包括表观遗传药物、靶向增强子的基因组编辑以及利用内源性调控逻辑的谱系特异性基因疗法。随着我们对红系表观基因组学理解的加深，我们设计针对红细胞疾病的合理、细胞类型特异性干预措施的能力也在增强。
