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

Tomokatsu Ikawa, Kyoko Masuda, Takaho A. Endo, Mitsuhiro Endo, Kyoichi Isono, Yoko Koseki, Rinako Nakagawa, Kohei Kometani, Junichiro Takano, Yasutoshi Agata, Yoshimoto Katsura, Tomohiro Kurosaki, Miguel Vidal, Haruhiko Koseki, Hiroshi Kawamoto

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2475-2485
Number of pages11
JournalGenes and Development
Volume30
Issue number22
DOIs
Publication statusPublished - 15-11-2016
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Genetics
  • Developmental Biology

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