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Cell competition regulates thymocyte turnover

ABSTRACT: Wild type thymi were transplanted into a competitive (wild type hosts), or non-competitive (Rag2-/-γc-/-KitW/Wv hosts) environment. Triple negative 2 and 3 (TN2/3) stages were sorted 14 days afetr transplantation and separated for cells of host or donor origin. Global gene expression data for TN2/3 cells, that were young, old with, and old without competition were compared.

ORGANISM(S): Mus musculus

SUBMITTER: Vera Martins

PROVIDER: E-GEOD-56418 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Cell competition is a tumour suppressor mechanism in the thymus.

Martins Vera C VC Busch Katrin K Juraeva Dilafruz D Blum Carmen C Ludwig Carolin C Rasche Volker V Lasitschka Felix F Mastitsky Sergey E SE Brors Benedikt B Hielscher Thomas T Fehling Hans Joerg HJ Rodewald Hans-Reimer HR

Nature 20140514 7501

Cell competition is an emerging principle underlying selection for cellular fitness during development and disease. Competition may be relevant for cancer, but an experimental link between defects in competition and tumorigenesis is elusive. In the thymus, T lymphocytes develop from precursors that are constantly replaced by bone-marrow-derived progenitors. Here we show that in mice this turnover is regulated by natural cell competition between 'young' bone-marrow-derived and 'old' thymus-reside ...[more]

PMID: 24828041

Similar Datasets

Cell competition regulates thymocyte turnover

Project description:Wild type thymi were transplanted into a competitive (wild type hosts), or non-competitive (Rag2-/-γc-/-KitW/Wv hosts) environment. Triple negative 2 and 3 (TN2/3) stages were sorted 14 days afetr transplantation and separated for cells of host or donor origin.

2014-05-16 | GSE56418 | GEO

Cell competition is a tumor suppressor mechanism in the thymus.

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-05-16 | E-GEOD-56419 | biostudies-arrayexpress

Intrathymic origins of T-ALL

Project description:Leukemia cells are considered developmentally 'frozen', and their phenotype is thought to reflect their stage of origin. To gain insights into the cell population from which T-ALL arises, we compared by global gene expression profiling T-ALL samples (n = 10) to different stages of T cell development, following the order from early thymic progenitor (ETP), to triple negative (TN) TN2, to TN3, to TN4, to immature single positive (ISP), to double positive (DP) thymocytes. Comparison of global gene expression between T-ALL samples and various stages of T cell development.

2014-05-16 | E-GEOD-56416 | biostudies-arrayexpress

Transcriptome analyses during disease progression

Project description:Transcriptome was assessed in the transitions from the normal thymus (with regular progenitor turnover), to a thymus devoid of extrinsic progenitor competition for 10 weeks, to fully malignant T cell acute lymphoblastic leukemia (T-ALL). Comparison of global gene expression between normal thymus, to thymus grafts with autonomous thymopoiesis, and T-ALL

2014-05-16 | E-GEOD-56417 | biostudies-arrayexpress

Overexpression of Lmo2 initiates T-lymphoblastic leukemia via impaired thymocyte competition.

Project description:Cell competition has recently emerged as an important tumor suppressor mechanism in the thymus that inhibits autonomous thymic maintenance. Here, we show that the oncogenic transcription factor Lmo2 causes autonomous thymic maintenance in transgenic mice by inhibiting early T cell differentiation. This autonomous thymic maintenance results in the development of self-renewing preleukemic stem cells (pre-LSCs) and subsequent leukemogenesis, both of which are profoundly inhibited by restoration of thymic competition or expression of the antiapoptotic factor BCL2. Genomic analyses revealed the presence of Notch1 mutations in pre-LSCs before subsequent loss of tumor suppressors promotes the transition to overt leukemogenesis. These studies demonstrate a critical role for impaired cell competition in the development of pre-LSCs in a transgenic mouse model of T cell acute lymphoblastic leukemia (T-ALL), implying that this process plays a role in the ontogeny of human T-ALL.

| S-EPMC10037042 | biostudies-literature

growth competition assay of Sendai virus and mumps virus

Project description:We evaluate the individual growth of 8 mutants of Sendai virus in the competitive condition under the cultured cells. We also evalate the growth of 6 mutants of mumps virus in the similar competitive condition.

2019-03-21 | GSE128625 | GEO

Blocking common gamma chain cytokine signaling ameliorates T-cell-mediated pathogenesis in disease models

Project description:The common γ chain (γc; IL2RG) is a subunit of the interleukin (IL) receptors for the γc cytokines IL2, IL4, IL7, IL9, IL15, and IL21. Because of the lack of appropriate neutralizing antibodies recognizing IL2RG, it has been difficult to thoroughly interrogate the role of γc cytokines in inflammatory and autoimmune disease settings. To determine whether γc cytokines might be targeted for T-cell-mediated disease prevention and treatment, we generated a new γc cytokine receptor antibody, REGN7257. Biochemical, structural and in vitro analysis showed that REGN7257 binds with high affinity to IL2RG and potently blocks signaling of all γc cytokines. In nonhuman primates, REGN7257 efficiently suppressed T-cells without impacting granulocytes, platelets or red blood cells. Using REGN7257, we showed that γc cytokines drive T-cell-mediated disease in mouse models of graft-versus-host disease (GVHD) and multiple sclerosis, by impacting multiple aspects of the pathogenic response. Importantly, we discovered that our xenogeneic GVHD mouse model recapitulates hallmarks of both acute and chronic GVHD, with T-cell expansion/infiltration into tissues and liver fibrosis, as well as hallmarks of immune aplastic anemia, with bone marrow aplasia and peripheral cytopenia. And we showed that γc cytokines contribute to disease pathology by driving all of these features. Overall, by demonstrating that broad inhibition of γc cytokine signaling with REGN7257 protects from immune-mediated disorders, our data provide evidence of γc cytokines as key drivers of pathogenic T-cell responses, offering a potentially novel strategy for the management of T-cell-mediated diseases.

2022-10-04 | GSE214625 | GEO

RNA Sequencing Analysis of Wild-type, Efferent Duct-Ligated, and W/Wv Caput Epididymal Transcriptomes

Project description:Purpose: The goal of this study is to detect differentially expressed genes, between wild-type (WT) efferent duct ligation (EDL)-treated, and W/Wv caput epididymis by RNA sequencing Methods: The EDL treatment of WT mice was performed from 10 weeks old and continued for 4 weeks until tissue sampling at 14 weeks old. Caput epididymal mRNA profiles of 14-week-old WT, EDL, and W/Wv mice were generated by deep sequencing, in triplicate, using Illumina NovaSeq6000. Results: RNA-seq data identified differentially expressed transcripts. Conclusions: Our results show that the expression of many genes was downregulated in EDL or W/Wv caput epididymis compared with WT one.

2023-05-23 | GSE232898 | GEO

Molecular evolution of sperm competition in mice

Project description:Sperm are amongst the most rapidly evolving cell types due, in part, to their central role in post-mating competitive reproductive success (sperm competition) and participation in coevolving male-female interactions. To establish the molecular basis of sperm divergence we have conducted a whole-cell, semi-quantitative proteomic approach to characterize sperm divergence in three closely related Mus species (musculus, spretus and spicilegus), which experience different regimes of sperm competition and exhibit remarkable variation in sperm production, energetics, motility and fertilization capacity.

2018-06-21 | PXD003376 | Pride

Expression analysis of Wv/Wv fetal gonads

Project description:Following sex determination, XY and XX gonads develop into a testis and an ovary, respectively. Depending on the sex of the gonad, resident germ cells will subsequently be committed to either spermatogenesis or oogenesis. In this study we took advantage of the Wv/Wv mouse genetic model, in which gonads are almost devoided of germ cells, to uncover gene expression underlying fetal germ cell development. Male and Female gonads were collected at 12, 14 and 16 days post coitum (dpc) from wild-type and Wv/Wv mouse embryos. Total RNAs were extracted and hybridized on Affymetrix microarrays. Expression signals from male and female gonads or from wild-type and mutant gonads were compared to identify sexually dimorphic genes as well as genes expressed in germ cell during fetal gonad development.

2010-12-20 | E-GEOD-23908 | biostudies-arrayexpress

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