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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.

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Transcriptome analyses during disease progression

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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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