Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNAi profiling of Arabidopsis knocked down and overexpressing CIN-TCP genes

ABSTRACT: Leaf development has been monitored chiefly by following anatomical markers. Analysis of transcriptome dynamics during leaf maturation revealed multiple expression patterns that rise or fall with age or that display age specific peaks. These were used to formulate a digital differentiation index (DDI), based on a set of selected markers with informative expression during leaf ontogeny. The leaf-based DDI reliably predicted the developmental state of leaf samples from diverse sources and was independent of mitotic cell division transcripts or propensity of the specific cell type. When calibrated by informative root markers, the same algorithm accurately diagnosed dissected root samples. We used the DDI to characterize plants with reduced activities of multiple CINCINNATA (CIN)-TCP growth regulators. These plants had giant curled leaves made up of small cells with abnormal shape, low DDI scores and low expression of mitosis markers, depicting the primary role of CIN-TCPs as promoters of differentiation. Delayed activity of several CIN-TCPs resulted in abnormally large but flat leaves with regular cells. The application of DDI has therefore portrayed the CIN-TCPs as heterochronic regulators that permit the development of a flexible and robust leaf form through an ordered and protracted maturation schedule. Experiment Overall Design: Vegetative apices of arabidopsis plants from modified CIN-TCP activity were collected. Experiment Overall Design: 1. Overexpression of an artificial microRNA targeting TCP5, TCP13 and TCP17 Experiment Overall Design: 2. Overexpression of the endogenous microRNA 319b targeting TCP2, TCP3, TCP4, TCP10 and TCP24 Experiment Overall Design: 3. the combination of the two microRNA, knocking down the eight CIN-TCP Experiment Overall Design: 4. Overexpression of TCP4 under the leaf specific BLS promoter

ORGANISM(S): Arabidopsis thaliana

SUBMITTER: Idan Efroni

PROVIDER: E-GEOD-12691 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

A protracted and dynamic maturation schedule underlies Arabidopsis leaf development.

Efroni Idan I Blum Eyal E Goldshmidt Alexander A Eshed Yuval Y

The Plant cell 20080919 9

Leaf development has been monitored chiefly by following anatomical markers. Analysis of transcriptome dynamics during leaf maturation revealed multiple expression patterns that rise or fall with age or that display age-specific peaks. These were used to formulate a digital differentiation index (DDI) based on a set of selected markers with informative expression during leaf ontogeny. The leaf-based DDI reliably predicted the developmental state of leaf samples from diverse sources and was indep ...[more]

PMID: 18805992

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Project description:Viral infections have a major impact on morbidity and mortality of immunosuppressed solid organ transplant (SOT) patients because of missing or failure of adequate pharmacologic antiviral treatment. Adoptive antiviral T-cell therapy (AVTT), regenerating disturbed endogenous T-cell immunity, emerged as an attractive alternative approach to combat severe viral complications in immunocompromised patients. AVTT is successful in patients after hematopoietic stem cell transplantation where T-cell products (TCPs) are manufactured from healthy donors. In contrast, in the SOT setting TCPs are derived from/applied back to immunosuppressed patients. We and others demonstrated feasibility of TCP generation from SOT patients and first clinical proof-of-concept trials revealing promising data. However, the initial efficacy is frequently lost long-term, because of limited survival of transferred short-lived T-cells indicating a need for next-generation TCPs. Our recent data suggest that Rapamycin treatment during TCP manufacture, conferring partial inhibition of mTOR, might improve its composition. The aim of this study was to confirm these promising observations in a setting closer to clinical challenges and to deeply characterize the next-generation TCPs. Using cytomegalovirus (CMV) as model, our next-generation Rapamycin-treated (Rapa-)TCP showed consistently increased proportions of CD4+ T-cells as well as CD4+ and CD8+ central-memory T-cells (TCM). In addition, Rapamycin sustained T-cell function despite withdrawal of Rapamycin and re-stimulation, showed superior T-cell viability and resistance to apoptosis, stable metabolism upon activation, preferential expansion of TCM, partial conversion of other memory T-cell subsets to TCM and increased clonal diversity. On transcriptome level, we observed a gene expression profile denoting long-lived early memory T-cells with potent effector functions. Furthermore, we successfully applied the novel protocol for the generation of Rapa-TCPs to 19/19 SOT patients in a comparative study, irrespective of their history of CMV reactivation. Moreover, comparison of paired TCPs generated before/after transplantation did not reveal inferiority of the latter despite exposition to maintenance immunosuppression post-SOT. Our data imply that the Rapa-TCPs, exhibiting longevity and sustained T-cell memory, are a reasonable treatment option for SOT patients. Based on our success to manufacture Rapa-TCPs from SOT patients under maintenance immunosuppression, now, we seek ultimate clinical proof of efficacy in a clinical study.

Dataset Information

RNAi profiling of Arabidopsis knocked down and overexpressing CIN-TCP genes

Publications

A protracted and dynamic maturation schedule underlies Arabidopsis leaf development.

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