Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from developing thymocytes of N15TCR transgenic Rag2 deficient mice

ABSTRACT: T cell development relies on the precise developmental control of various cellular functions for appropriate positive and negative selection. Previously, gene expression profiling of peptide-driven negative selection events in the N15 TCR class I MHC-restricted mouse and D011.10 TCR class II MHC-restricted mouse has offered insights into the coordinate engagement of biological processes affecting thymocyte development. However, there has been little comparable detailed in vivo global genome expression analysis reported for positive selection. We used microarrays to identify the genes differentially expressed during CD8 single positive T cell development in N15 TCR transgenic Rag2 deficient mice. We have analyzed gene expression in the individual populations as development proceeds from DP, intermediate (Int), to SP subsets. To this end, we sorted the individual populations from six age and sex matched 5-6 week old N15 TCR tg+/+ RAG-2-/- H-2b mice for two independent experiments. For sorting subpopulations, cells were stained with anti-CD4 (L3T4) and anti-CD8 (Ly-2) antibodies (Pharmingen, San Diego, CA USA) and DP, Int and SP thymocytes were sorted on a MoFlo (Cytomation, Fort Collins, CO USA).

ORGANISM(S): Mus musculus

SUBMITTER: Young Choi

PROVIDER: E-GEOD-13493 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla.

Choi Young I YI Duke-Cohan Jonathan S JS Ahmed Wesam B WB Handley Maris A MA Mann Fanny F Epstein Jonathan A JA Clayton Linda K LK Reinherz Ellis L EL

Immunity 20081127 6

Precise intrathymic cell migration is important for thymocyte maturation and organ architecture. The orchestration of thymocyte trafficking, however, is not well understood at a molecular level. Here, we described highly regulated plexinD1 expression on CD4+CD8+ double positive (DP) thymocytes. PlexinD1 expression was further affected by the engagement of T cell receptor complex. Activation of plexinD1 via the ligand, semaphorin 3E, repressed CCL25 chemokine signaling via its receptor CCR9 in CD ...[more]

PMID: 19027330

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Project description:Developmental checkpoints in stem/progenitor cells are critical to the determination, commitment and differentiation into distinct lineages. Cancer cells often retain expression of lineage-specific checkpoint proteins, but their potential impact in cancer remains elusive. T lymphocytes mature in the thymus following a highly orchestrated developmental process that entails the successive rearrangements and expression of T-cell receptor (TCR) genes. Low affinity recognition of self-peptide/MHC complexes (self-pMHC) presented by thymic epithelial cells by the TCR of CD4+CD8+ (DP) cortical thymocytes transduces positive selection signals that ultimately shape the developing T cell repertoire. DP thymocytes not receiving these signals die by lack of stimulation whereas those that recognize self-pMHC with high affinity undergo TCR-mediated apoptosis and negative selection. In T-cell acute lymphoblastic leukaemia (T-ALL), leukaemic transformation of maturating thymocytes results from the acquisition of multiple genetic and epigenetic alterations in oncogenes and tumour suppressor genes, that disrupt the normal regulatory circuits and drive clonal expansion of differentiation-arrested lymphoblasts. We show here that TCR triggering by negatively-selecting self-pMHC prevented T-ALL development and leukaemia maintenance in mice. Induction of TCR signalling by high affinity self-pMHC or treatment with monoclonal antibodies to the CD3 signalling chain (anti-CD3) caused massive leukaemic cell death and a gene expression program resembling that of thymocyte negative selection. Importantly, anti-CD3 treatment hampered leukaemogenesis in mice transplanted with either mouse or patient-derived T-ALLs. These data provide a rationale for targeted therapy based on anti-CD3 treatment of T-ALL patients and demonstrate that endogenous developmental checkpoint proteins are amenable to therapeutic intervention in cancer cells. Gene expression data from four culture conditions was performed for the following cells: ALL-SIL-TCRÎ±/Î²-GFP co-cultured on OP9-DL1 for 48 h, ALL-SIL-TCRÎ±/Î²-GFP without co-culture, ALL-SIL cells transduced with TLX shRNA (sh-TLX), and ALL-SIL transduced with sh-control vectors. All conditions are performed in two replicates.

Dataset Information

Expression data from developing thymocytes of N15TCR transgenic Rag2 deficient mice

Publications

PlexinD1 glycoprotein controls migration of positively selected thymocytes into the medulla.

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