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Transcription factor Hoxb5 reprograms B cells into functional T lymphocytes. Nat Immunol 2018 03;19(3):279-290

Date

02/13/2018

Pubmed ID

29434353

Pubmed Central ID

PMC6190911

DOI

10.1038/s41590-018-0046-x

Scopus ID

2-s2.0-85041891411   15 Citations

Abstract

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.

Author List

Zhang M, Dong Y, Hu F, Yang D, Zhao Q, Lv C, Wang Y, Xia C, Weng Q, Liu X, Li C, Zhou P, Wang T, Guan Y, Guo R, Liu L, Geng Y, Wu H, Du J, Hu Z, Xu S, Chen J, He A, Liu B, Wang D, Yang YG, Wang J

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
B-Lymphocytes
Cell Differentiation
Cell Lineage
Cellular Reprogramming
Homeodomain Proteins
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Inbred NOD
Mice, SCID
Precursor Cells, B-Lymphoid
T-Lymphocytes
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5