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Trap1a is an X-linked and cell-intrinsic regulator of thymocyte development.


ABSTRACT: The X-linked Trap1a gene encodes the tumor rejection antigen P1A, which is expressed in fetal tissues and multiple lineages of tumor cells. The function of this gene remains unknown. Using chimeric mice with wild-type (WT) and Trap1a-/y bone marrow, we show that Trap1a-/y donor cells are capable of generating most lineages of hematopoietic cells, with the notable exception of T cells. Deletion of Trap1a selectively arrests T-cell development at double-negative stage 1 (DN1, with a CD4-CD8-CD25-CD44+ phenotype). Because Trap1a is expressed in Lin-Sca-1+c-Kit+ and common lymphoid progenitors but not in immature thymocytes (DN1-DN4), Trap1a mutations affect the differentiation potential of progenitor cells without directly acting on T cells. Despite a similarity in the blockade of DN1 to DN2 transition, the Trap1a-/y DN1 cells have normal expression of c-Kit, in contrast to what was reported in the Notch1-/- DN1. Complementary DNA profiling of Trap1a-/y and WT embryonic stem cells shows that Trap1a does not regulate the Notch pathway. Our data reveal that Trap1a is an X-linked regulator that affects the differentiation potential of progenitor cells into T cells through a Notch-independent mechanism and identify an important function for the Trap1a gene.

SUBMITTER: Li CS 

PROVIDER: S-EPMC5549601 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Trap1a is an X-linked and cell-intrinsic regulator of thymocyte development.

Li Chi-Shan CS   Tang Fei F   Zhang Peng P   Jiang Taijiao T   Saunders Thomas L TL   Zheng Pan P   Liu Yang Y  

Cellular & molecular immunology 20160411 8


The X-linked Trap1a gene encodes the tumor rejection antigen P1A, which is expressed in fetal tissues and multiple lineages of tumor cells. The function of this gene remains unknown. Using chimeric mice with wild-type (WT) and Trap1a<sup>-/y</sup> bone marrow, we show that Trap1a<sup>-/y</sup> donor cells are capable of generating most lineages of hematopoietic cells, with the notable exception of T cells. Deletion of Trap1a selectively arrests T-cell development at double-negative stage 1 (DN1,  ...[more]

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