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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Transcriptome analyses during disease progression

ABSTRACT: 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

ORGANISM(S): Mus musculus

SUBMITTER: Vera Martins

PROVIDER: E-GEOD-56417 | 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

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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

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

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. Global gene expression data for TN2/3 cells, that were young, old with, and old without competition were compared.

2014-05-16 | E-GEOD-56418 | 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).

2014-05-16 | GSE56417 | GEO

Generation of a functional, patient specific human thymus from induced pluripotent stem cell in vivo

Project description:Here we describe a universal direct differentiation protocol that allows the generation of thymic epithelial progenitor cells (TEPs) from different iPSC lines. Upon transplantation into an athymic mouse model, TEPs further differentiate into thymic epithelial cells (TECs). TECs are functional and can facilitate the education of developing mouse T-cells. iPSC derived, patient specific TECs residing within grafts are indistinguishable from TECs present in human primary neonatal thymus tissue as revealed by single cell RNA sequencing analysis indicating the generation of a mature TEC phenotype. Taken together, we provide a universal direct differentiation protocol that generates TEPs from all iPSC lines tested, that can further differentiate into mature, functional TECs. We anticipate that these findings have important implications for current efforts aimed at generating a functional human thymus.

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Thymic epithelial cell potency and fate in early organogenesis assessed by single cell transcriptional and functional analysis. [10x Genomics]

Project description:During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population is mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency, and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells.

2023-06-20 | GSE229248 | GEO

Thymic epithelial cell potency and fate in early organogenesis assessed by single cell transcriptional and functional analysis [Smart-Seq2]

Project description:During development, cortical (c) and medullary (m) thymic epithelial cells (TEC) arise from the third pharyngeal pouch endoderm. Current models suggest that within the thymic primordium most TEC exist in a bipotent/common thymic epithelial progenitor cell (TEPC) state able to generate both cTEC and mTEC, at least until embryonic day 12.5 (E12.5) in the mouse. This view, however, is challenged by recent transcriptomics and genetic evidence. We therefore set out to investigate the fate and potency of TEC in the early thymus. Here using single cell (sc) RNAseq we identify a candidate mTEC progenitor population at E12.5, consistent with recent reports. Via lineage-tracing we demonstrate this population is mTEC fate-restricted, validating our bioinformatics prediction. Using potency analyses we also establish that most E11.5 and E12.5 progenitor TEC are cTEC-fated. Finally, we show that overnight culture causes most if not all E12.5 cTEC-fated TEPC to acquire functional bipotency and provide a likely molecular mechanism for this changed differentiation potential. Collectively, our data overturn the widely held view that a common TEPC predominates in the E12.5 thymus, showing instead that sublineage-primed progenitors are present from the earliest stages of thymus organogenesis but that these early fetal TEPC exhibit cell-fate plasticity in response to extrinsic factors. Our data provide a significant advance in understanding of fetal thymic epithelial development and thus have implications for thymus-related clinical research, in particular research focussed on generating TEC from pluripotent stem cells.

2023-06-21 | GSE232765 | GEO

Expression data for haploid Saccharomyces cerevisiae strains growing in a defined low glucose medium.

Project description:We used microarrays to assess differences in gene expression associated with single nucleotide polymorphisms occurred in three genes, PMA1, MDS3 and MKT1, as compared to a reference strain devoid of any mutations (Progenitor strain). Haploid yeast strains carrying no evolved alleles (progenitor - reference strain) or different combinations of the studied evolved alleles (PMA1e, MDS3e and MKT1e) and devoid of all other evolved alleles were used. The following genotypes were studied: ancestral, MDS3e, MKT1e, MDS3e_MKT1e and PMA1e_MKT1e (2 replicates each). Cells of the studied strains were grown overnight on liquid yeast peptone dextrose (YPD) medium and used to inoculate defined low glucose medium.

2011-05-20 | E-GEOD-29353 | biostudies-arrayexpress

De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids

Project description:Hematopoietic humanized (hu) mice are powerful tools for modeling the action of human immune system and are widely used for preclinical studies and drug discovery. However, generating a functional human T cell compartment in hu mice remains challenging, primarily due to the species-related differences between human and mouse thymus. While engrafting human fetal thymic tissues can support robust T cell development in hu mice, tissue scarcity and ethical concerns limit their wide use. Here, we describe the tissue engineering of human thymus organoids from inducible pluripotent stem cells (iPSC-thymus) that can support the de novo generation of a diverse population of functional human T cells. T cells of iPSC-thymus engrafted hu mice could mediate both cellular and humoral immune responses, including mounting robust proinflammatory responses upon TCR engagement, inhibiting the growth of allogeneic tumor grafts and facilitating efficient Ig class switching. Our findings suggest that hu mice engrafted with iPSC-thymus can serve as a novel animal model to study human T cell-mediated immunity and accelerate the translation of animal studies into the clinic.

2022-05-31 | GSE201675 | GEO

Expression data for haploid Saccharomyces cerevisiae strains growing in a defined low glucose medium.

2011-05-20 | GSE29353 | GEO

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