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Conversion of T cells to B cells by inactivation of polycomb-mediated epigenetic
suppression of the B-lineage program
#MMPMID27913604
Ikawa T
; Masuda K
; Endo TA
; Endo M
; Isono K
; Koseki Y
; Nakagawa R
; Kometani K
; Takano J
; Agata Y
; Katsura Y
; Kurosaki T
; Vidal M
; Koseki H
; Kawamoto H
Genes Dev
2016[Nov]; 30
(22
): 2475-2485
PMID27913604
show ga
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.
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