Correlative controls (influences of one organ over another organ) of seeds over maternal growth are one of the most obvious phenotypic expressions of the trade-off between growth and reproduction. However, the underlying molecular mechanisms are largely unknown. Here, we characterize the physiological and molecular effects of correlative inhibition by seeds on Arabidopsis thaliana inflorescences, i.e. global proliferative arrest (GPA) during which all maternal growth ceases upon the production of a given number of seeds. We use laser-assisted microdissection and RNA-seq or Affymetrix GeneChip hybridizations to compare sterile growing, fertile growing and fertile arrested meristems or whole inflorescences. In shoot tissues, we detected the induction of stress- and senescence-related gene expression upon fruit production and GPA, and a drop in chlorophyll levels - suggestive of altered source-sink relationships between vegetative shoot and reproductive tissues. Levels of shoot reactive oxygen species, however, strongly decreased upon GPA - a phenomenon that is associated with bud dormancy in some perennials. Indeed, gene expression changes in arrested apical inflorescences after fruit removal resembled changes observed in axillary buds following release from apical dominance. This suggests that GPA represents a form of bud dormancy, and that dominance is gradually transferred from growing inflorescences to maturing seeds - allowing offspring control over maternal resources, simultaneously restricting offspring number.
Seed Production Affects Maternal Growth and Senescence in Arabidopsis.
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View SamplesCell type specific transcriptome analysis from laser microdissected megaspore mother cells (MMC) from Arabidopsis thaliana (L.) Heynh., accession Landsberg erecta.
Transcriptome analysis of the Arabidopsis megaspore mother cell uncovers the importance of RNA helicases for plant germline development.
Sex, Specimen part, Subject
View SamplesNucellus tissue surrounding the megaspore mother cell in Arabidopsis thaliana (L.) Heynh. , accession Landsberg erecta, isolated by laser assisted microdissection
Transcriptome analysis of the Arabidopsis megaspore mother cell uncovers the importance of RNA helicases for plant germline development.
Specimen part, Subject
View Samplesdifferential expression between wild-type pistils of Arabidopsis thaliana at late 11 to late 12 floral stages, and similar stage pistils of coatlique mutant which lacks a functional embryo sac
Genetic subtraction profiling identifies genes essential for Arabidopsis reproduction and reveals interaction between the female gametophyte and the maternal sporophyte.
Specimen part
View SamplesSenescence can be transmitted in a paracrine way from cells undergoing Oncogene Induced Senescence (OIS) to nave normal cells. We define this phenomenon as paracrine senescence
A complex secretory program orchestrated by the inflammasome controls paracrine senescence.
Specimen part, Cell line
View SamplesAID-dependent U/G mismatches in S DNA are converted by BER and MMR DNA pathways into double-stranded breaks that are required for optimal CSR in activated B cells. Deficits in MMR proteins, MSH2, MLH1, and PMS2 result in lower CSR frequencies that are coupled with impaired DSB formation. MBD4 interacts with MLH1 and has been postulated to coordinate mismatch repair of U/G. Deletions of Mbd4 targeting the 5' end of the gene in mice do not affect CSR . However, Mbd4 transcription is complex, with the propensity to create alternative transcripts, including residual transcription leading to to truncated protein expression that complicates ananlysis in these mice. We describe a novel function of MBD4 housed in the C-terminus that is critical for DSB formation, which shares several characteristics with MMR . We conclude that the 3' end of the Mbd4 gene positively contributes to CSR and likely intersects the MMR pathway.
MBD4 Facilitates Immunoglobulin Class Switch Recombination.
Cell line, Treatment
View SamplesRecent studies have shown that the RNA binding protein Musashi 2 (Msi2) plays prominent roles during development and leukemia. Additionally, in embryonic stem cells (ESC) undergoing the early stages of differentiation, Msi2 has been shown to associate with Sox2, which is required for the self-renewal of ESC. These findings led us to examine the effects of Msi2 on the behavior of ESC. Using an shRNA sequence that targets Msi2 and a scrambled shRNA sequence, we determined that knockdown of Msi2 disrupts the self-renewal of ESC and promotes their differentiation. Collectively, our findings argue that Msi2 is required to support the self-renewal and pluripotency of ESC.
Musashi2 is required for the self-renewal and pluripotency of embryonic stem cells.
Specimen part, Cell line
View SamplesWe generated mice with a transgenic BAC on a B6 background. The BAC contains Glo1, and the transgenic mice were found to overexpress Glo1.
Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal.
Sex, Specimen part
View SamplesWe used laser capture microdissection to isolate both microvascular endothelial cells and neurons from post mortem brain tissue from patients with schizophrenia and bipolar disorder and healthy controls. RNA was isolated from these cell populations, amplified, and analysed using Affymetrix HG133plus2.0 GeneChips. In the first instance, we used the dataset to compare the neuronal and endothelial data, in order to demonstrate that the predicted differences between cell types could be detected using this methodology.
The cerebral microvasculature in schizophrenia: a laser capture microdissection study.
Specimen part
View SamplesThe number of long-term survivors of high-risk neuroblastoma remains discouraging, with 10-year survival as low as 20%, despite decades of considerable international efforts to improve outcome. Major obstacles remain and include managing resistance to induction therapy, which causes tumor progression and early death in high-risk patients, and managing chemotherapy-resistant relapses, which can occur years after the initial diagnosis. Identifying and validating novel therapeutic targets is essential to improve treatment. Delineating and deciphering specific functions of single histone deacetylases in neuroblastoma may support development of targeted acetylome-modifying therapeutics for patients with molecularly defined high-risk neuroblastoma profiles. We show here that HDAC11 depletion in MYCN-driven neuroblastoma cell lines strongly induces cell death, mostly mediated by apoptotic programs. Genes necessary for mitotic cell cycle progression and cell division were most prominently enriched in at least two of three time points in whole-genome expression data combined from two cell systems, and all nine genes in these functional categories were strongly repressed, including CENPA, KIF14, KIF23 and RACGAP1. Enforced expression of one selected candidate, RACGAP1, partially rescued the induction of apoptosis caused by HDAC11 depletion. High-level expression of all nine genes in primary neuroblastomas signicantly correlated with unfavorable overall and event-free survival in patients, suggesting a role in mediating the more aggressive biological and clinical phenotype of these tumors. Our study identied a group of cell cycle-promoting genes regulated by HDAC11, being both predictors of unfavorable patient outcome and essential for tumor cell viability. The data indicates a signicant role of HDAC11 for mitotic cell cycle progression and survival of MYCN-amplified neuroblastoma cells, and suggests that HDAC11 could be a valuable drug target.
Neuroblastoma cells depend on HDAC11 for mitotic cell cycle progression and survival.
Cell line, Time
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