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FBXL 12 regulates T‐cell differentiation in a cell‐autonomous manner
Author(s) -
Nita Akihiro,
Nishiyama Masaaki,
Muto Yoshiharu,
Nakayama Keiichi I.
Publication year - 2016
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12360
Subject(s) - biology , aldehyde dehydrogenase , stem cell , cellular differentiation , microbiology and biotechnology , embryonic stem cell , cell type , trophoblast , null cell , cell , cell culture , placenta , fetus , biochemistry , genetics , gene , pregnancy
Aldehyde dehydrogenase ( ALDH ) activity is a hallmark of stem cells including embryonic, adult tissue and cancer stem cells. The SCF FBXL 12 complex is an authentic ubiquitin ligase that targets ALDH 3 for degradation. FBXL 12 is essential for the differentiation of trophoblast stem cells into specific cell types in the placenta during mouse embryogenesis, but its physiological functions in adult tissues have remained unknown. We have now investigated the role of the FBXL 12‐ ALDH 3 axis in the thymus, in which FBXL 12 was most abundant among adult mouse tissues examined. During T‐cell differentiation, FBXL 12 is most abundant in CD 4 + CD 8 + ( DP ) cells, with its expression declining as these cells differentiate into CD 4 + CD 8 − or CD 4 − CD 8 + ( SP ) cells. T cells of FBXL 12‐null mice manifested a differentiation block at the DP – SP transition that was associated with ALDH 3 accumulation in DP cells. This differentiation block was also apparent in wild‐type mouse recipients of FBXL 12‐null bone marrow transplants as well as in FBXL 12‐null fetal thymic organ culture, suggesting that it is a cell‐autonomous phenomenon in the thymus rather than an indirect effect of altered systemic conditions. Our results thus indicate that, in addition to its role in placental development, the FBXL 12‐ ALDH 3 axis is required for maturation of undifferentiated thymocytes.