Cell-cell communication is critical for stem cell maintenance. Shoot apical meristem (SAM) located at the shoot tip harbors stem cells within the central zone (CZ). Their progeny differentiate in the adjacent peripheral zone (PZ). WUSCHEL (WUS) is a homeodomain transcription factor produced in a few cells of the organizing center (OC), located beneath the CZ. It has been shown to specify stem cell fate and also activate CLAVATA3 (CLV3) expression in cells of the CZ. CLV3 is a secreted peptide that activates a membrane bound receptor kinase-CLAVATA1 to restrict WUS transcription to the OC. It has been hypothesized that WUS activates CLV3 expression and stem cell fate in adjacent cells of the CZ by activating a non-cell autonomous signal. Contrary to this hypothesis, here we show that the WUS protein after being synthesized in cells of the OC, migrates into the superficial cell layers of the CZ where it activates CLV3 transcription by binding to its promoter elements. WUS also migrates laterally into the PZ to repress the expression of differentiation promoting transcription factors by binding to their regulatory regions. Migration of a stem cell inducing transcription factor into adjacent cells to activate a negative regulator, whereby restricting its own accumulation is unique to plant stem cell niches. While stem cell promoting transcription factor directly repressing differentiation promoting transcription factors to prevent premature differentiation of stem cell progenitors is conserved among diverse stem cell niches.
Plant stem cell maintenance involves direct transcriptional repression of differentiation program.
Treatment
View SamplesPolarity defects are a hallmark of most carcinomas. Cells from invasive micropapillary carcinomas (IMPCs) of the breast are characterized by a striking cell polarity inversion and represent a good model for the analysis of polarity abnormalities. We have performed an in-depth investigation of polarity alterations in 24 IMPCs, compared with invasive carcinomas of no special type (ICNST).
LIN7A is a major determinant of cell-polarity defects in breast carcinomas.
Specimen part
View SamplesPurpose: The objective of this study was to determine cardiac transcriptional pathways regulated in response to 1.) hypothyroidism and re-establishment of a euthyroid state and 2.) Med13-dependent cardiac transcriptional pathways regulated in response to hypothyroidism and re-establishment of a euthyroid state Overall design: Methods: WT and Med13 cardiac-specific knockout mice (Med13cKO) were put on a normal chow or PTU diet at 8 weeks of age for a duration of 4 weeks. A third group was put on a PTU diet for 4 weeks followed by 3 daily injections of T3.
Regulation of cardiac transcription by thyroid hormone and Med13.
No sample metadata fields
View SamplesAnalysis of ventricular derived mRNA from Med1fl/fl and Med1fl/fl cardiac knockout mice. Results provide insight into the molecual rmechanisms underlying dilated cardiomyopathy. Overall design: Methods: Ventricular samples (4 per group) from 21-day-old Med1fl/fl and Med1 cardiac knockout mice were used to generate polyA enriched stranded RNA libraries followed by RNAseq using the Illumina HiSeq platform. Raw sequence reads were analyzed with BaseSpace (www.illumina.com) by aligning reads to the mus musculus mm10 genome using the TopHat Alignment app. Transcripts were assembled and significant differentially expressed genes were determined with the Cufflinks Assembly and DE app using a false discovery rate <0.05. qRT–PCR validation was performed using SYBR Green assays
Cardiac Med1 deletion promotes early lethality, cardiac remodeling, and transcriptional reprogramming.
Specimen part, Subject
View SamplesHuman transcripts can typically be processed at multiple polyadenylation sites to yield mRNA isoforms with distinct 3 ends. A multitude of factors contributes to the choice of individual polyadenylation sites in different cell types and tissues. In this study we have found that the heterogenous ribonucleoprotein C (hnRNP C), an RNA binding protein that was previously linked to splicing and polyadenylation at Alu repeat elements, is a general regulator of pre-mRNA cleavage and polyadenylation. By sequencing mRNA 3 ends from cells expressing normal and reduced levels of hnRNP C we found that transcripts that contain poly(U) tracts around their poly(A) sites respond in a manner indicative of hnRNP C repressing cleavage and polyadenylation. The 3 UTR isoforms whose abundance is modulated by hnRNP C contain U-rich elements and can thereby interact with A/U-rich element binding proteins that have been shown to alter transcript stability, sub-cellular localization and even the localization of the translated proteins.
A comprehensive analysis of 3' end sequencing data sets reveals novel polyadenylation signals and the repressive role of heterogeneous ribonucleoprotein C on cleavage and polyadenylation.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Medullary Breast Carcinoma, a Triple-Negative Breast Cancer Associated with BCLG Overexpression.
Disease, Disease stage
View SamplesGene expression was compared between medullary breast carcinoma (MBC) and non medullary basal-like breast carcinoma (non-MBC BLC).
Medullary Breast Carcinoma, a Triple-Negative Breast Cancer Associated with BCLG Overexpression.
Disease, Disease stage
View SamplesMicroarray Analysis of Space-flown Murine Thymus Tissue Reveals Changes in Gene Expression Regulating Stress and Glucocorticoid Receptors. We used microarrays to detail the gene expression of space-flown thymic tissue and identified distinct classes of up-regulated genes during this process. We report here microarray gene expression analysis in young adult C57BL/6NTac mice at 8 weeks of age after exposure to spaceflight aboard the space shuttle (STS-118) for a period of 13 days. Upon conclusion of the mission, thymus lobes were extracted from space flown mice (FLT) as well as age- and sex-matched ground control mice similarly housed in animal enclosure modules (AEM). mRNA was extracted and an automated array analysis for gene expression was performed. Examination of the microarray data revealed 970 individual probes that had a 1.5 fold or greater change. When these data were averaged (n=4), we identified 12 genes that were significantly up- or down-regulated by at least 1.5 fold after spaceflight (p0.05). Together, these data demonstrate that spaceflight induces significant changes in the thymic mRNA expression of genes that regulate stress, glucocorticoid receptor metabolism, and T cell signaling activity. These data explain, in part, the reported systemic compromise of the immune system after exposure to the microgravity of space.
Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors.
Specimen part
View SamplesHuman Natural Killer (NK) cells comprise two main subsets, CD56bright and CD56dim cells, that differ in function, phenotype and tissue localization. To further dissect the heterogeneity of CD56dim cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56dim CD62L+ cells. Indeed, only these cells combine the ability to produce interferon (IFN)-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56dim CD62L+ cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK cell subsets into immunodeficient mice suggest that CD56dim CD62L+ cells represent an intermediate stage of NK cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors.
CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells.
Specimen part
View SamplesLeanness is associated with increased lifespan and is linked to favorable metabolic conditions promoting life extension.
Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice.
Sex, Specimen part
View Samples