Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic suppression of the B-lineage program

12 p.-6 fig.1 tab.Tomokatsu Ikawa, et al.
In general, cell fate is determined primarily by transcription factors, followed by epigenetic mechanisms fixing the status. While the importance of transcription factors controlling cell fate has been well characterized, epigenetic regulation of cell fate maintenance remains to be elucidated. Here we provide an obvious fate conversion case, in which the inactivation of polycomb-medicated epigenetic regulation results in conversion of T-lineage progenitors to the B-cell fate. In T-cell-specific Ring1A/B-deficient mice, T-cell development was severely blocked at an immature stage. We found that these developmentally arrested T-cell precursors gave rise to functional B cells upon transfer to immunodeficient mice. We further demonstrated that the arrest was almost completely canceled by additional deletion of Pax5. These results indicate that the maintenance of T-cell fate critically requires epigenetic suppression of the B-lineage gene program.
This work was supported in part by grants from the Japan Society for the Promotion of Science (24689042 to T.I.), the Japan Science and Technology Agency (T.I.), RIKEN Center for Integrative Medical Sciences (IMS) Young Chief Investigator program (T.I.), and the Kanae Foundation for the Promotion of Medical Science (T.I.).