Gata1/FLI1重编程B淋巴细胞生成巨核细胞样细胞OA
Gata1/FLI1-mediated reprogramming of B lymphocytes into megakaryocyte-like cells
血小板短缺是临床实践中的常见问题,基于细胞重编程的工程化血小板制备技术是解决该难题的一种潜在方案.本研究以B淋巴细胞为起始细胞,探索通过转录因子Gata1和FLI1驱动细胞重编程生成巨核细胞的可能性.研究发现,通过过表达转录因子Gata1,部分小鼠原代B淋巴细胞能够被诱导表达巨核细胞特异性标志物Cd41和Cd42,显示其向巨核细胞样细胞转分化的潜力.进一步研究表明,共表达FLI1和Gata1或使用Ezh2/Ezh1抑制剂UNC1999处理,均可显著提高细胞重编程效率.重编程细胞经过10~14 d培养,部分细胞呈现前血小板形态特征.值得注意的是,过表达BCR-ABL诱导的永生化B淋巴细胞仍保持对Gata1/FLI1诱导的响应性.综上所述,本研究表明B淋巴细胞具有重编程为巨核细胞的潜力,有望成为工程化血小板制备的起始细胞.此外,由于B淋巴细胞具备悬浮培养特性,并且在永生化过程中仍保持对重编程因子的响应性,基于B淋巴细胞的重编程体系可能在实际应用中更易于实现大规模制备.
Platelet shortages are a common issue in clinical practice,and the growing demand for platelet transfusions has made this problem even more prominent.Platelets generated through cell reprogramming may provide a promising solution to address this critical challenge.Here,we report that enforced expression of transcription factors Gata1 and FLI1 reprograms murine bone marrow B lymphocytes into megakaryocytes.Notably,the expression of Gata1 alone in B lymphocytes was sufficient to induce the activation of megakaryocyte-specific markers,such as Cd41 and Cd42.Co-expression of FLI1 or treatment with the Ezh2/Ezh1 inhibitor UNC1999 significantly enhanced reprogramming efficiency.After 10-14 days,the reprogrammed cells acquired megakaryocyte morphology,and some cells proceeded to form pro-platelets.Importantly,we found that B lymphocytes retain their plasticity even after immortalization,this maybe the reason that Gata1/FLI1 could reprogram both primary and BCR-ABL-immortalized B lymphocytes.These findings suggest that B lymphocytes are a promising starting cell type for generating platelets through cell reprogramming and may be more suitable for large-scale production compared to adherent cells due to their suspension growth characteristics.
朱俊先;袁紫慧;胡志月;姚红;谢华锋
华南理工大学医学院,广东 广州 510006华南理工大学医学院,广东 广州 510006华南理工大学医学院,广东 广州 510006华南理工大学医学院,广东 广州 510006华南理工大学医学院,广东 广州 510006
生物科学
B淋巴细胞细胞重编程巨核细胞UNC1999
B lymphocytescell reprogrammingmegakaryocyteUNC1999
《中山大学学报(自然科学版)(中英文)》 2026 (2)
88-98,11
国家自然科学基金(31970625)
评论