Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes

作者：Zhang, Mengyun; Dong, Yong; Hu, Fangxiao; Yang, Dan; Zhao, Qianhao; Lv, Cui; Wang, Ying; Xia, Chengxiang; Weng, Qitong; Liu, Xiaofei; Li, Chen; Zhou, Peiqing; Wang, Tongjie; Guan, Yuxian; Guo, Rongqun; Liu, Lijuan; Geng, Yang; Wu, Hongling; Du, Juan; Hu, Zheng; Xu, Sheng; Chen, Jiekai; He, Aibin; Liu, Bing; Wang, Demin; Yang, Yong-Guang; Wang, Jinyong

来源：Nature Immunology, 2018, 19(3): 279-+.

DOI：10.1038/s41590-018-0046-x

• HEMATOPOIETIC STEM-CELLS
• GENE
• EXPRESSION
• FETAL
• PAX5
• DIFFERENTIATION
• CHROMATIN
• RECONSTITUTION
• REARRANGEMENT
• IDENTITY

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.

• 单位
  中国人民解放军第二军医大学; 中国人民解放军军事医学科学院; 福建师范大学; 中国科学院大学; 吉林大学; 蛋白质组学国家重点实验室; 中国科学院广州生物医药与健康研究院; 医学免疫学国家重点实验室; 北京大学