Alternative splicing (AS) is a key process underlying the expansion of proteomic diversity and the regulation of gene expression. However, the contribution of AS to the control of embryonic stem cell (ESC) pluripotency is not well understood. Here, we identify an evolutionarily conserved ESC-specific AS event that changes the DNA binding preference of the forkhead family transcription factor FOXP1. We show that the ESC-specific isoform of FOXP1 stimulates the expression of transcription factor genes required for pluripotency including OCT4, NANOG, NR5A2 and GDF3, while concomitantly repressing genes required for ESC differentiation. Remarkably, this isoform also promotes the maintenance of ESC pluripotency and the efficient reprogramming of somatic cells to induced pluripotent stem cells. These results thus reveal that an AS switch plays a pivotal role in the regulation of pluripotency and functions by controlling critical ESC-specific transcriptional programs. Overall design: Exons 18 and 18b form a mutually exclusive splicing event. The FOXP1 (non-ES) isoform contains only exon 18 and not 18b, while the FOXP1-ES isoform contains only exon 18b and not 18. To investigate whether FOXP1 and FOXP1-ES control different sets of genes, we performed knockdowns using custom siRNA pools targeting FOXP1 exons 18 or 18b in undifferentiated H9 cells, followed by RNA-Seq profiling.
An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming.
Specimen part, Subject
View SamplesWe used RNA-seq and Ribo-seq analyses to examine the effect of CPT treatment of translation efficiency (TE) Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) using biological duplicates of control and CPT-treated (5 hrs) MCF7 cells
Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation.
No sample metadata fields
View SamplesWe used RNA-seq and Ribo-seq analyses to examine translation efficiency (TE) in PC9 and H1933 cells Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) in PC9 and H1933 cell lines
Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation.
No sample metadata fields
View SamplesWe used RNA-seq and Ribo-seq analyses to examine the effect of Nutlin3a (activator of p53) treatment of translation efficiency (TE) Overall design: We measured expression levels (RNA.seq) and ribosome densities (ribo-seq) in control and Nutlin3a-treated (20 hrs) MCF7 cells
Transcription Impacts the Efficiency of mRNA Translation via Co-transcriptional N6-adenosine Methylation.
No sample metadata fields
View SamplesEfferent inhibition of cochlear outer hair cells is mediated by nicotinic cholinergic receptors containing alpha9 (a9) and alpha10 subunits. Mice lacking a9 nicotinic subunits fail to exhibit classic olivocochlear responses and are characterized by abnormal synaptic morphology at the base of outer hair cells. To detail molecular changes induced upon the loss of a9 subunit, we sampled cochlear RNA from wild type and a9 null mice at postnatal (P) days spanning periods of synapse formation and maturation (P3, P7, P13 and P60). Our findings point to a delay in cochlear maturation starting at the onset of hearing (P13), as well as an up-regulation of various GABA receptor subunits in adult mice lacking the a9 nicotinic subunit.
Lack of nAChR activity depresses cochlear maturation and up-regulates GABA system components: temporal profiling of gene expression in alpha9 null mice.
Specimen part
View SamplesBackground: Transposable elements are known to influence the regulation of some genes. We aimed to determine which genes show altered gene expression when transposable elements are epigenetically activated.
Genome-wide identification of genes regulated in trans by transposable element small interfering RNAs.
Specimen part
View SamplesAmniotic fluid (AF) is a complex biological material that provides a unique window into the developing human. Residual AF supernatant contains cell-free fetal RNA. The objective of this study was to develop an understanding of the AF core transcriptome by identifying the transcripts ubiquitously present in the AF supernatant of euploid midtrimester fetuses.
The amniotic fluid transcriptome: a source of novel information about human fetal development.
Sex
View SamplesWhole brain irradiation remains important in the management of brain tumors. Although necessary for improving survival outcomes, cranial irradiation also results in cognitive decline in long-term survivors. A chronic inflammatory state characterized by microglial activation has been implicated in radiation-induced brain injury, and here we present a comprehensive transcriptional profile of irradiated microglia.
Aging-like changes in the transcriptome of irradiated microglia.
Age, Specimen part
View SamplesDuring pregnancy, cells from each fetus travel into the maternal circulation and organs, resulting in the development of microchimerism. Identification of the cell types in this microchimeric population would permit better understanding of possible mechanisms by which they affect maternal health. However, comprehensive analysis of fetal cells has been hampered by their rarity. In this study, we sought to overcome this obstacle by combining flow cytometry with multidimensional gene expression microarray analysis of fetal cells isolated from the murine maternal lung during late pregnancy. Fetal cells were collected from the lungs of pregnant female mice. cDNA was amplified and hybridized to gene expression microarrays. The resulting fetal cell core transcriptome was interrogated using multiple methods including Ingenuity Pathway Analysis, the BioGPS gene expression database, principal component analysis, the Eurexpress gene expression atlas and primary literature. Here we report that small numbers of fetal cells can be flow sorted from the maternal lung, facilitating discovery-driven gene expression analysis. We additionally show that gene expression data can provide functional information about the fetal cells. Our results suggest that fetal cells in the murine maternal lung are a mixed population, consisting of trophoblasts, mesenchymal stem cells and cells of the immune system. The detection of trophoblasts and immune cells in the maternal lung may facilitate future mechanistic studies related to the development of immune tolerance and pregnancy-related complications, such as preeclampsia. Furthermore, the presence and persistence of mesenchymal stem cells in maternal organs may have implications for long-term postpartum maternal health.
Comprehensive analysis of genes expressed by rare microchimeric fetal cells in the maternal mouse lung.
No sample metadata fields
View SamplesBackground: Turner syndrome, a common sex chromosome aneuploidy, has characteristics and malformations associated with the phenotype. Fetal amniotic fluid is a complex biological material that could contribute to the understanding Turner syndrome pathogenesis. Global gene expression analysis of Turner syndrome fetal amniotic fluid supernatant was utilized to identify organ systems and specific genes that may play a role in the pathophysiologic changes that are seen in individuals with Turner syndrome.
Amniotic fluid RNA gene expression profiling provides insights into the phenotype of Turner syndrome.
No sample metadata fields
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