CAS Key Laboratory of Regenerative Biology and Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Immunol. 2018 Mar;19(3):279-290. doi: 10.1038/s41590-018-0046-x. Epub 2018 Feb 12.
Deletion of master regulators of the B cell lineage reprograms B cells into T cells. Here we found that the transcription factor Hoxb5, which is expressed in uncommitted hematopoietic progenitor cells but is not present in cells committed to the B cell or T cell lineage, was able to reprogram pro-pre-B cells into functional early T cell lineage progenitors. This reprogramming started in the bone marrow and was completed in the thymus and gave rise to T lymphocytes with transcriptomes, hierarchical differentiation, tissue distribution and immunological functions that closely resembled those of their natural counterparts. Hoxb5 repressed B cell 'master genes', activated regulators of T cells and regulated crucial chromatin modifiers in pro-pre-B cells and ultimately drove the B cell fate-to-T cell fate conversion. Our results provide a de novo paradigm for the generation of functional T cells through reprogramming in vivo.
缺失 B 细胞谱系的主调控因子可将 B 细胞重编程为 T 细胞。在这里，我们发现转录因子 Hoxb5 可将前 B 祖细胞重编程为功能性早期 T 细胞谱系祖细胞，该因子在未定向造血祖细胞中表达，但不存在于定向 B 细胞或 T 细胞谱系的细胞中。这种重编程始于骨髓，并在胸腺中完成，产生的 T 淋巴细胞具有转录组、层次分化、组织分布和免疫学功能，与天然 T 淋巴细胞非常相似。Hoxb5 抑制 B 细胞“主基因”，激活 T 细胞调控因子，并调控前 B 祖细胞中的关键染色质修饰因子，最终驱动 B 细胞命运向 T 细胞命运转变。我们的研究结果为体内重编程生成功能性 T 细胞提供了一个新的范例。
