This SuperSeries is composed of the SubSeries listed below.
Genome-wide analysis reveals conserved transcriptional responses downstream of resting potential change in Xenopus embryos, axolotl regeneration, and human mesenchymal cell differentiation.
Sex, Specimen part
View SamplesDepolarization of resting membrane potential in select cells in Xenopus larvae induces striking hyperpigmentation due to dysregulation of melanocytes. Here, we show that this non-cell-autonomous process is mediated by cAMP, CREB, and the transcription factors Sox10 and Slug. Our microarray analysis reveals specific transcripts responsive to Vmem levels within a few hours of depolarization, and a set of 517 transcripts whose expression remains altered during the full hyperpigmented phenotype over a week later, linking instructor cell-depolarization to a range of developmental processes and disease states. We also show that voltage-dependent conversion of melanocytes involves the MSH-secreting melanotrope cells of the pituitary, and formulate a model for the molecular pathway linking the bioelectric properties of melanocyte cells microenvironment in vivo to the genetic and cellular changes induced in this melanoma-like phenotype. Remarkably, the phenotype is all-or-none: each individual animal either undergoes melanocyte conversion or not, as a whole. This group decision is stochastic, resulting in varying percentages of hyperpigmented individuals for a given experimental treatment. To understand the stochasticity and dynamic properties of this complex signaling system, we developed a novel computational method that automates the reverse-engineering of stochastic dynamic signaling models. We used this method to discover a network model that quantitatively explained our complex dataset, and even made correct predictions for new experiments that we validated in vivo. Taken together, these data (1) reveal new molecular details about a novel trigger of metastatic-like developmental cell behavior in vivo, (2) suggest new targets for biomedical intervention, and (3) demonstrate proof-of-principle of a computational method for understanding stochastic decision-making by cells during embryonic development and metastasis.
Serotonergic regulation of melanocyte conversion: A bioelectrically regulated network for stochastic all-or-none hyperpigmentation.
Specimen part
View SamplesChromosome dosage plays a significant role in reproductive isolation and speciation in both plants and animals, but underlying mechanisms are largely obscure. Transposable elements can promote hybridity through maternal small RNA, and have been postulated to regulate dosage response via neighboring imprinted genes. Here, we show that a highly conserved microRNA in plants, miR845, targets the tRNAMet primer-binding site (PBS) of LTR-retrotransposons in Arabidopsis pollen, and triggers the accumulation of 21 to 22-nucleotide small RNA in a dose dependent fashion via RNA polymerase IV. We show that these epigenetically activated small-interfering RNAs (easiRNAs) mediate hybridization barriers between diploid seed parents and tetraploid pollen parents (“the triploid block”), and that natural variation for miR845 may account for “endosperm balance” allowing formation of triploid seeds. Targeting the PBS with small RNA is a common mechanism for transposon control in mammals and plants, and provides a uniquely sensitive means to monitor chromosome dosage and imprinting in the developing seed. Overall design: RNA-seq of Arabidopsis pollen
Transposon-derived small RNAs triggered by miR845 mediate genome dosage response in Arabidopsis.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy.
No sample metadata fields
View SamplesAnalysis of genes that were differentially expressed in mutant VUB03_DM1 as compared to controls VUB01 and SA01 Neural Precursor cells
Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy.
No sample metadata fields
View SamplesAnalysis of genes that were differentially expressed in mutant VUB03_DM1 as compared to controls VUB01 and SA01 undifferentiated hES cells
Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy.
No sample metadata fields
View SamplesAnalysis of genes that were differentially expressed in mutant VUB03_DM1 as compared to controls VUB01 and SA01 Mesodermal Precursors Cells.
Mutant human embryonic stem cells reveal neurite and synapse formation defects in type 1 myotonic dystrophy.
No sample metadata fields
View SamplesHere we used microarray expression profiling to characterise global changes in gene expression during stages of proliferation and differentiation of human neural stem cells
Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
DIDO as a Switchboard that Regulates Self-Renewal and Differentiation in Embryonic Stem Cells.
Specimen part
View SamplesTransition from symmetric to asymmetric cell division requires precise coordination of differential gene expression. Embryonic stem cells (ESC) strongly express Dido3, whose C-terminal truncation impedes ESC differentiation while retaining self-renewal. We show that Dido3 binds to its gene locus via H3K4me3 and RNA pol II and, at differentiation onset, induces expression of its splice variant Dido1, which then leads to Dido3 degradation and downregulation of stemness genes. We propose that Dido isoforms act as a switchboard to regulate genetic programs for ESC transition from pluripotency maintenance to promotion of differentiation.
DIDO as a Switchboard that Regulates Self-Renewal and Differentiation in Embryonic Stem Cells.
Specimen part
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