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SRP052568
Mus musculus
4 Downloadable Samples
Description
Cell fate specification relies on the action of critical transcription factors that become available at distinct stages of embryonic development. One such factor is NeuroD1, which is essential for eliciting the neuronal development program and possesses the ability to reprogram other cell types into neurons. Given this capacity, it is important to understand its targets and the mechanism underlying neuronal specification. Here, we show that NeuroD1 directly binds regulatory elements of neuronal genes that are developmentally silenced by epigenetic mechanisms. This targeting is sufficient to initiate events that confer transcriptional competence, including reprogramming of transcription factor landscape, conversion of heterochromatin to euchromatin and increased chromatin accessibility, indicating potential pioneer factor ability of NeuroD1. The transcriptional induction of neuronal fate genes is maintained via epigenetic memory despite a transient NeuroD1 induction during neurogenesis. Our study not only reveals the NeuroD1-dependent gene regulatory program driving neurogenesis but also increases our understanding of how cell-fate specification during development involves a concerted action of transcription factors and epigenetic mechanisms. Overall design: 1. Ectopic NeuroD1 was induced for 48 hours (+Dox) in ES cells for checking initiation of neuronal transcriptional program in comparison to uninduced condition (-Dox) 2. ChIP-seq was performed after 24 hours of NeuroD1 induction in ES cells.
Publication Title
NeuroD1 reprograms chromatin and transcription factor landscapes to induce the neuronal program.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Analyze the function of the transcription factors Hand2 and Gata3 in adult sympathetic neurons by induced knockout and RNAseq analysis Overall design: Method and Result: Hand2flx/del::DbhCreERT2 (referred to as mutant) and Hand2flx/+::DbhCreERT2 (referred to a control) were injected for 10 days with tamoxifen to activate Cre. Animals were killed, sympathetic ganglia (SCG+Stellate) collected and processed for RNA isolation and RNAseq (Stanzel et al., 2016). Gata3flx/flx::DbhCerERT2 (mutant) and Gata3flx/+::DbhCreERT2 (controls) were treated as Hand2 animals. 16 ganglia from 4 mice were pooled for Hand2 mutant and controls and Gata3 controls. As only rudimentary ganglia were present in Gata3 mutant mice (Tsarovina et al., 2010) ganglia from 8 mice were pooled. The specific effects of the Hand2 knockout are decribed in Stanzel et al., 2016. The analysis of ganglion rudiments in the Gata3 knockout revealed that Gata3 was not reduced, indicating that the remaining cells had escaped the knockout.
Publication Title
Distinct roles of hand2 in developing and adult autonomic neurons.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 769 Downloadable Samples
- Illumina HiSeq 2500
Description
Ectopic expression of defined transcription factors can force direct cell fate conversion from one lineage to another in the absence of cell division. Several transcription factor cocktails have enabled successful reprogramming of various somatic cell types into induced neurons (iNs) of distinct neurotransmitter phenotype. However, the nature of the intermediate states that drive the reprogramming trajectory towards distinct iN types is largely unknown. Here we show that successful direct reprogramming of adult human brain pericytes into functional iNs by Ascl1 and Sox2 (AS) encompasses transient activation of a neural stem cell-like gene expression program that precedes bifurcation into distinct neuronal lineages. Intriguingly, during this transient state key signaling components relevant for neural induction and neural stem cell maintenance are regulated and functionally contribute to iN reprogramming and maturation. Thus, AS-mediated reprogramming into a broad spectrum of iN types involves the unfolding of a developmental program via neural stem cell-like intermediates. Overall design: Single-cell transcriptomes from multiple time points and conditions during direct conversion of human pericytes into induced pericytes through the overexpression of defined factors. Please note that [1] the *ctrl samples represent mock-transfected cells (analyzed along side of the transfected cells) [2] The cell type (for each sample) is provided as 'pericytes or pericyte-derived induced neuronal cells' (as they are in a differentiation continuum from pericytes to neurons due to the treatment protocol) with the combination of 'genotype/variation' and 'time point' information.
Publication Title
Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gamma tocotrienol induces apoptosis in breast cancer cells however, the molecular mechanisms are not completely understood.
Publication Title
Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
MiR-1246 was found to promote tumorigenesis and metastasis in sevearl cancer types. In the context of tumor microenvironment, tumor-associated macrophages are a central part typically correlated with poor prognosis.
Publication Title
Mutant p53 cancers reprogram macrophages to tumor supporting macrophages via exosomal miR-1246.
Sample Metadata Fields
Specimen part
View Samples- Escherichia coli
- 4 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
A study on the effects of an sdiA mutant and the AHL molecule on the virulence of EHEC
Publication Title
Chemical sensing in mammalian host-bacterial commensal associations.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 1000
Description
Epithelial-neuronal signaling is essential for sensory encoding in touch, itch and nociception; however, little is known about the release mechanisms and neurotransmitter receptors through which skin cells govern neuronal excitability. Merkel cells are mechanosensory epidermal cells that have long been proposed to activate neuronal afferents through chemical synaptic transmission. We employed a set of classical criteria for chemical neurotransmission as framework to directly test this hypothesis. RNA sequencing of adult Merkel cells demonstrated that they express presynaptic molecules and biosynthetic machinery for adrenergic transmission. Moreover, live-cell imaging directly demonstrated that Merkel cells mediate activity- and VMAT-dependent release of fluorescent catecholamine neurotransmitter analogues. Touch-evoked firing in Merkel-cell afferents was inhibited either by pre-synaptic silencing of SNARE-mediated vesicle release from Merkel cells or by neuronal deletion of b2-adrenergic receptors. Together, these results identify both pre- and postsynaptic mechanisms through which Merkel cells excite mechanosensory afferents to encode gentle touch. Overall design: RNA-seq of basal keratinocytes and Merkel cells purified with FACS
Publication Title
Merkel Cells Activate Sensory Neural Pathways through Adrenergic Synapses.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Primary culture airway epithelial cells, grown under physiologic air-liquid interface conditions, with, or without IL-13 in order to study the effects of this cytokine on mucous cell metaplasia, an important feature of asthma and COPD.
Publication Title
IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 105 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Prostate cancer (PCa) tends to be more aggressive and lethal in African Americans (AA) compared to European Americans (EA). To further understand the biological factors accounting for the PCa disparities observed in AA and EA patients, we performed gene profiling using Affymetrix human exon 1.0 ST arrays to identify the differentially expressed genes beween AA cancer and patient matched normal tissues.
Publication Title
Identification and Functional Validation of Reciprocal microRNA-mRNA Pairings in African American Prostate Cancer Disparities.
Sample Metadata Fields
Specimen part
View Samples