Author:
Ikawa Tomokatsu,Masuda Kyoko,Endo Takaho A.,Endo Mitsuhiro,Isono Kyoichi,Koseki Yoko,Nakagawa Rinako,Kometani Kohei,Takano Junichiro,Agata Yasutoshi,Katsura Yoshimoto,Kurosaki Tomohiro,Vidal Miguel,Koseki Haruhiko,Kawamoto Hiroshi
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.
Funder
Japan Society for the Promotion of Science
Japan Science and Technology Agency
Integrative Medical Sciences
Young Chief Investigator program
Kanae Foundation for the Promotion of Medical Science
Publisher
Cold Spring Harbor Laboratory
Subject
Developmental Biology,Genetics
Cited by
29 articles.
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