Del Burgo Fernando Gutiérrez, García-López María Ángeles, Pons Tirso, de Luis Enrique Vázquez, Martínez-A Carlos, Villares Ricardo
Centro Nacional de Biotecnología/CSIC, Darwin 3, Cantoblanco, E-28049, Madrid, Spain.
Centro Nacional de Investigaciones Cardiovasculares, Instituto de Salud Carlos III, Melchor Fernández Almagro 3, 28029, Madrid, Spain.
Cell Biosci. 2025 Apr 26;15(1):56. doi: 10.1186/s13578-025-01394-x.
The development of hematopoietic cell lineages is a highly complex process governed by a delicate interplay of various transcription factors. The expression of these factors is influenced, in part, by epigenetic signatures that define each stage of cell differentiation. In particular, the formation of B lymphocytes depends on the sequential silencing of stemness genes and the balanced expression of interdependent transcription factors, along with DNA rearrangement. We have investigated the impact of Dido3 deficiency, a protein involved in chromatin status readout, on B cell differentiation within the hematopoietic compartment of mice. Our findings revealed significant impairments in the successive stages of B cell development. The absence of Dido3 resulted in remarkable alterations in the expression of essential transcription factors and differentiation markers, which are crucial for orchestrating the differentiation process. Additionally, the somatic recombination process, responsible for generation of antigen receptor diversity, was also adversely affected. These observations highlight the vital role of epigenetic regulation, particularly the involvement of Dido3, in ensuring proper B cell differentiation. This study reveals new mechanisms underlying disruptive alterations, deepening our understanding of hematopoiesis and may potentially lead to insights that aid in the development of therapeutic interventions for disorders involving aberrant B cell development.
造血细胞谱系的发育是一个高度复杂的过程，受多种转录因子之间微妙的相互作用所调控。这些因子的表达部分受到定义细胞分化各个阶段的表观遗传特征的影响。特别是，B淋巴细胞的形成依赖于干性基因的顺序沉默、相互依赖的转录因子的平衡表达以及DNA重排。我们研究了参与染色质状态读取的蛋白质Dido3缺陷对小鼠造血系统中B细胞分化的影响。我们的研究结果显示，B细胞发育的连续阶段存在显著缺陷。Dido3的缺失导致了对协调分化过程至关重要的关键转录因子和分化标志物表达的显著改变。此外，负责产生抗原受体多样性的体细胞重组过程也受到了不利影响。这些观察结果突出了表观遗传调控的重要作用，特别是Dido3的参与，以确保B细胞的正常分化。这项研究揭示了破坏性改变背后的新机制，加深了我们对造血作用的理解，并可能潜在地带来有助于开发针对涉及异常B细胞发育疾病的治疗干预措施的见解。
