Filters
Technology
Platform
SRP094632
Mus musculus
4 Downloadable Samples
Illumina HiSeq 2500
Description
The mechanisms that activate some genes while silencing others are critical to ensure precision in lineage specification as multipotent progenitors become restricted in cell fate. During neurodevelopment, these mechanisms are required to generate the wide variety of neuronal subtypes found in the nervous system. Here we report interactions between basic helix-loop-helix (bHLH) transcriptional activators and the transcriptional repressor PRDM13 that are critical for these processes during specification of dorsal spinal cord neurons. PRDM13 inhibits gene expression programs for the excitatory neuronal lineages in the dorsal neural tube while also suppressing a battery of genes that determine ventral neural tube fates including Olig1, Olig2 and Prdm12. PRDM13 does this via recruitment to chromatin by multiple neural bHLH factors to restrict gene expression in specific neuronal lineages. Together these findings highlight the function of PRDM13 in repressing bHLH transcriptional activators that together are required to achieve precise neuronal specification during development. Overall design: RNA-seq analysis performed on GFP+ cells sorted by FACS from Prdm13GFP/+ or Prdm13GFP/GFP mouse E11.5 neural tubes to identify gene expression in the presence and absence of PRDM13.
Publication Title
Repression by PRDM13 is critical for generating precision in neuronal identity.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
The proper balance of excitatory and inhibitory neurons is crucial to normal processing of somatosensory information in the dorsal spinal cord. Two neural basic helix-loop-helix transcription factors, Ascl1 and Ptf1a, are essential for generating the correct number and sub-type of neurons in multiple regions of the nervous system. Â In the dorsal spinal cord, Ascl1 and Ptf1a have contrasting functions in specifying inhibitory versus excitatory neurons. To understand how Ascl1 and Ptf1a function in these processes, we identified their direct transcriptional targets genome-wide in the embryonic mouse neural tube using ChIP-Seq and RNA-Seq. We show that Ascl1 and Ptf1a regulate the specification of excitatory and inhibitory neurons in the dorsal spinal cord through direct regulation of distinct homeodomain transcription factors known for their function in neuronal sub-type specification. Besides their roles in regulating these homeodomain factors, Ascl1 and Ptf1a each function differently during neuronal development with Ascl1 directly regulating genes with roles in several steps of the neurogenic program including, Notch signaling, neuronal differentiation, axon guidance, and synapse formation. In contrast, Ptf1a directly regulates genes encoding components of the neurotransmitter machinery in inhibitory neurons, and other later aspects of neural development distinct from those regulated by Ascl1. Moreover, Ptf1a represses the excitatory neuronal fate by directly repressing several targets of Ascl1. Examination of the Ascl1 and Ptf1a bound sequences shows they are enriched for a common E-Box with a GC core and with additional motifs used by Sox, Rfx, Pou, and Homeodomain factors. Ptf1a bound sequences are uniquely enriched in an E-Box with a GA/TC core and in the binding motif for its co-factor Rbpj, providing two keys to specificity of Ptf1a binding. The direct transcriptional targets identified for Ascl1 and Ptf1a provide a molecular understanding for how they function in neuronal development, particularly as key regulators of homeodomain transcription factors required for neuronal sub-type specification. Overall design: Examination of gene expression in Ascl1 and Ptf1a lineage cells in the developing neural tube.
Publication Title
A transcription factor network specifying inhibitory versus excitatory neurons in the dorsal spinal cord.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
We found that the cancer testis antigen, ZNF165, is required for viability and can modulate TGF-induced gene expression in mesenchymal, Claudin-Low, TNBC. We employed the Affymetrix microarray platform to uncover transcriptionally modulated genes following ZNF165 depletion and TGF stimulation using the Claudin-low TNBC tumor-derived cell lines, SUM159 as a model. Our results provide insight into how ZNF165 globally modulates TGF signaling.
Publication Title
Comprehensive functional characterization of cancer-testis antigens defines obligate participation in multiple hallmarks of cancer.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Prostate cancer is a leading cause of cancer death amongst males. The main clinical dilemma in treating prostate cancer is the high number of indolent cases that confer a significant risk of over diagnosis and over treatment. In this study we have performed a genome expression profiling of tumor tissue specimens from 36 patients with prostate cancer to identify transcripts that delineate aggressive and indolent cancer. We included normal prostate biopsies from 14 patients in our analysis. Unsupervised hierarchical cluster analysis separated the cancer samples into two groups with a significant overrepresentation of tumors from patients with biochemical recurrence in one of the groups (Chi2, p=0.02). The samples were separated by basically three clusters of genes that showed differential expression between the two sample clusters - totaling 371 transcripts. Ingenuity Pathway Analysis revealed that one cluster contained genes associated with invasive properties of the tumor, another genes associated with the cell cycle, and the last cluster genes involved in several biological functions. We successfully validated the transcripts association with recurrence using two publicly available patient datasets totaling 669 patients. Twelve genes were found to be independent predictors of recurrence in multivariate logistical regression analysis.
Publication Title
Expression profiling of prostate cancer tissue delineates genes associated with recurrence after prostatectomy.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a) associated with changes in mRNA expression reflecting estrogenic actions and/or b) dependent on the estrogen receptor (ER), we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2) on fetal mammary tissues of wild type and ER knock-out mice.
Publication Title
Low-dose BPA exposure alters the mesenchymal and epithelial transcriptomes of the mouse fetal mammary gland.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The mechanisms instructing genesis of neuronal subtypes from mammalian neural precursors are not well-understood. To address this issue, we have characterized the transcriptional landscape of radial glial precursors (RPs) in the embryonic murine cortex. We show that individual RPs express mRNA but not protein for transcriptional specifiers of both deep and superficial layer cortical neurons. Some of these mRNAs, including the superficial versus deep layer neuron transcriptional regulators Brn1 and Tle4, are translationally repressed by their association with the RNA-binding protein Pumilio2 and the 4E-T protein. When these repressive complexes are disrupted in RPs mid-neurogenesis by knocking down 4E-T or Pum2, this causes aberrant co-expression of deep layer neuron specification proteins in newborn superficial neurons. Thus, cortical RPs are transcriptionally primed to generate diverse types of neurons, and a 4E-T-Pum2 complex represses translation of some of these neuronal identity mRNAs to ensure appropriate temporal specification of daughter neurons.
Publication Title
A Translational Repression Complex in Developing Mammalian Neural Stem Cells that Regulates Neuronal Specification.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 7 Downloadable Samples
- NextSeq 500
Description
Adult neural stem cells (NSCs) derive from embryonic precursors, but little is known about how or when this occurs. We have addressed this issue using single cell RNAseq at multiple developmental timepoints to analyze the embryonic murine cortex, one source of adult forebrain NSCs. We computationally identify all major cortical cell types, including the embryonic radial precursors (RPs) that generate adult NSCs. We define the initial emergence of RPs from neuroepithelial stem cells at E11.5. We show that by E13.5 these RPs express a transcriptional identity that is maintained and reinforced throughout their transition to a non-proliferative state between E15.5 and E17.5. These slowly-proliferating late embryonic RPs share a core transcriptional phenotype with quiescent adult forebrain NSCs. Together, these findings support a model where cortical RPs maintain a core transcriptional identity from embryogenesis through to adulthood, and where the transition to a quiescent adult NSC occurs during late neurogenesis. Overall design: We applied the high-throughput single-cell mRNA sequencing technique, Drop-seq, to the embryonic mouse cortex. 2000-5000 single cells from wildtype CD1 embryos of gestational ages E11.5, E13.5, E15.5 and E17.5 were characterized.
Publication Title
Developmental Emergence of Adult Neural Stem Cells as Revealed by Single-Cell Transcriptional Profiling.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The neural stem cell decision to self-renew or differentiate is tightly regulated by its microenvironment. Here, we have asked about this microenvironment, focusing on growth factors in the embryonic cortex at a time when it is largely comprised of neural precursor cells (NPCs) and newborn neurons. We show that cortical NPCs secrete factors that promote their maintenance while cortical neurons secrete factors that promote differentiation. To define factors important for these activities, we used transcriptome profiling to identify ligands produced by NPCs and neurons, cell surface mass spectrometry to identify receptors on these cells, and computational modeling to integrate these data. The resultant model predicts a complex growth factor environment with multiple autocrine and paracrine interactions. We tested this communication model, focusing on neurogenesis, and identified IFN, Nrtn and glial-derived neurotrophic factor (GDNF) as ligands with unexpected roles in promoting neurogenic differentiation of NPCs in vivo.
Publication Title
Proneurogenic Ligands Defined by Modeling Developing Cortex Growth Factor Communication Networks.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
T4 and T5 neurons are components of the neuronal circuit for motion vision in flies. To identify genes involved in neuronal computation of T4 and T5 neurons, we perfomed transcriptome analysis. Nuclei of T4 and T5 neurons were immunoprecipitated, total RNA was harvested and used for mRNA-seq with Illumina technology. In two biological replicates, we mapped 154 and 119 million reads to D. melanogaster genome. mRNA-seq provided information about expression levels of 17,468 annotated transcripts in the T4 and T5 neurons. Overall design: Cell type – specific transcriptome analysis of the RNA isolated from immunoprecipitated nuclei, performed in two biological replicates
Publication Title
RNA-Seq Transcriptome Analysis of Direction-Selective T4/T5 Neurons in Drosophila.
Sample Metadata Fields
Subject
View Samples