title: 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-/ybone marrow, we show that Trap1a-/ydonor 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-/yand 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.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, China.
authors.forename: Chi-Shan
authors.initials: CS
authors.lastname: Li
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Tang
authors.affiliation: Institute of Biophysics, Chinese Academy of Science, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Institute of Biophysics, Chinese Academy of Science, Beijing, China.
authors.forename: Taijiao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Department of Internal Medicine, School of Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Saunders
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Zheng
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism; D001854:Bone Marrow Cells / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D050172:Genes, X-Linked / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*; D060168:Thymocytes / Q000502:physiology*; D018183:Transplantation Chimera
chemical_list: D000951:Antigens, Neoplasm; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; C507749:cancer-testis antigen P1A, mouse; D019009:Proto-Oncogene Proteins c-kit