Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA228926 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1030510.fastq.gz | Fastqsanger.gz | |||
| SRR1030503.fastq.gz | Fastqsanger.gz | |||
| SRR1030504.fastq.gz | Fastqsanger.gz | |||
| SRR1030505.fastq.gz | Fastqsanger.gz | |||
| SRR1030506.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 8 |
Similar Datasets
Project description:Switch Enhancer Elements Control Cell Fate in Human Embryonic Stem Cells (BeadChip)
| PRJNA228930 | ENA
Project description:Enhancers play key roles in gene regulation. However, comprehensive enhancer discovery is challenging because most enhancers, especially those affected in complex diseases, have weak effects on gene expression. Through gene regulatory network modeling, we identified that dynamic cell state transitions, a critical missing component in prevalent enhancer discovery strategies, can be utilized to improve the cells’ sensitivity to enhancer perturbation. Guided by the modeling results, we performed a mid-transition CRISPRi-based enhancer screen utilizing human embryonic stem cell definitive endoderm differentiation as a dynamic transition system. The screen discovered a comprehensive set of enhancers (4 to 9 per locus) for each of the core lineage-specifying transcription factors (TFs), including many enhancers with weak to moderate effects. Integrating the screening results with enhancer activity measurements (ATAC-seq, H3K27ac ChIP-seq) and three-dimensional enhancer-promoter interaction information (CTCF looping, Hi-C), we were able to develop a CTCF loop-constrained Interaction Activity (CIA) model that can better predict functional enhancers compared to models that rely on Hi-C-based enhancer-promoter contact frequency. Together, our dynamic network-guided enhancer screen and the CIA enhancer prediction model provide generalizable strategies for sensitive and more comprehensive enhancer discovery in both normal and pathological cell state transitions.
2023-06-17 | PXD043070 | Pride
Project description:<p>Non-coding elements in our genomes that play critical roles in complex disease are frequently marked by highly unstable RNA species. Sequencing nascent RNAs attached to an actively transcribing RNA polymerase complex can identify unstable RNAs, including those templated from gene-distal enhancers (eRNAs). However, nascent RNA sequencing techniques remain challenging to apply in some cell lines and especially to intact tissues, limiting broad applications in fields such as cancer genomics and personalized medicine. Here we report the development of chromatin run-on and sequencing (ChRO-seq), a novel run-on technology that maps the location of RNA polymerase using virtually any frozen tissue sample, including samples with degraded RNA that are intractable to conventional RNA-seq. We used ChRO-seq to develop the first maps of nascent transcription in 23 human glioblastoma (GBM) brain tumors and patient derived xenografts. Remarkably, >90,000 distal enhancers discovered using the signature of eRNA biogenesis within primary GBMs closely resemble those found in the normal human brain, and diverge substantially from GBM cell models. Despite extensive overall similarity, 12% of enhancers in each GBM distinguish normal and malignant brain tissue. These enhancers drive regulatory programs similar to the developing nervous system and are enriched for transcription factor binding sites that specify a stem-like cell fate. These results demonstrate that GBMs largely retain the enhancer landscape associated with their tissue of origin, but selectively adopt regulatory programs that are responsible for driving stem-like cell properties. We also identified enhancers and their associated transcription factors that regulate genes characteristic of each known GBM subtype, and discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study uncovers new insights into the molecular etiology of GBM and introduces ChRO-seq which can now be used to map regulatory programs contributing to a variety of complex diseases.</p>
| phs001646 | dbGaP
Project description:A small toolkit of morphogens is used repeatedly to direct development, raising the question of how context dictates interpretation of the same cue. One example is the TGFβ pathway that in human embryonic stem cells fulfills two opposite functions: pluripotency maintenance and mesendoderm (ME) specification. Using proteomics coupled to analysis of genome occupancy, we uncover a regulatory complex comprised of transcriptional effectors of the Hippo pathway (TAZ/YAP/TEAD), the TGFβ pathway (SMAD2/3) and the pluripotency regulator OCT4 (TSO). TSO collaborates with NuRD repressor complexes to buffer pluripotency gene expression, while suppressing ME genes. Importantly, the SMAD DNA binding partner FOXH1, a major specifier of ME, is found near TSO elements and upon fate specification we show that TSO is disrupted with subsequent SMAD-FOXH1 induction of ME. These studies define switch enhancer elements and provide a framework to understand how cellular context dictates interpretation of the same morphogen signal in development. Total RNA was isolated from human embryonic stem cells (WA09) 48h after siRNA transfection (siCntr, siTAZ/YAP, siTEAD1-4)
2013-12-18 | E-GEOD-52439 | biostudies-arrayexpress
Project description:A small toolkit of morphogens is used repeatedly to direct development, raising the question of how context dictates interpretation of the same cue. One example is the TGFβ pathway that in human embryonic stem cells fulfills two opposite functions: pluripotency maintenance and mesendoderm (ME) specification. Using proteomics coupled to analysis of genome occupancy, we uncover a regulatory complex comprised of transcriptional effectors of the Hippo pathway (TAZ/YAP/TEAD), the TGFβ pathway (SMAD2/3) and the pluripotency regulator OCT4 (TSO). TSO collaborates with NuRD repressor complexes to buffer pluripotency gene expression, while suppressing ME genes. Importantly, the SMAD DNA binding partner FOXH1, a major specifier of ME, is found near TSO elements and upon fate specification we show that TSO is disrupted with subsequent SMAD-FOXH1 induction of ME. These studies define switch enhancer elements and provide a framework to understand how cellular context dictates interpretation of the same morphogen signal in development. ChIP experiment, a total of 8 samples: 4 samples DMSO treated (Input ctr, IgG ctr, SMAD2 precipitation, TEAD4 precipitation), 4 samples SB431542 (Input ctr, IgG ctr, SMAD2 precipitation, TEAD4 precipitation)
2013-12-18 | E-GEOD-52437 | biostudies-arrayexpress
Project description:Chickarmane2006 - Stem cell switch reversible
Kinetic modeling approach of the transcriptional dynamics of the embryonic stem cell switch.
This model is described in the article:
Transcriptional dynamics of the embryonic stem cell switch.
Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C
PLoS Computational Biology. 2006; 2(9):e123
Abstract:
Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched on/off by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is on, the self-renewal genes are on and the differentiation genes are off. The opposite holds when the switch is off. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the switch remains on even when the activating signal is removed. Hence, the stem cell can be manipulated to be self-renewing without the requirement of input signals. We also suggest tests that could discriminate between a variety of feedforward regulation architectures of the target genes by OCT4, SOX2, and NANOG.
This model is hosted on BioModels Database
and identified by: MODEL7957907314
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000203 | BioModels
Project description:Chickarmane2006 - Stem cell switch irreversible
Kinetic modeling approach of the transcriptional dynamics of the embryonic stem cell switch.
This model is described in the article:
Transcriptional dynamics of the embryonic stem cell switch.
Chickarmane V, Troein C, Nuber UA, Sauro HM, Peterson C
PLoS Computational Biology. 2006; 2(9):e123
Abstract:
Recent ChIP experiments of human and mouse embryonic stem cells have elucidated the architecture of the transcriptional regulatory circuitry responsible for cell determination, which involves the transcription factors OCT4, SOX2, and NANOG. In addition to regulating each other through feedback loops, these genes also regulate downstream target genes involved in the maintenance and differentiation of embryonic stem cells. A search for the OCT4-SOX2-NANOG network motif in other species reveals that it is unique to mammals. With a kinetic modeling approach, we ascribe function to the observed OCT4-SOX2-NANOG network by making plausible assumptions about the interactions between the transcription factors at the gene promoter binding sites and RNA polymerase (RNAP), at each of the three genes as well as at the target genes. We identify a bistable switch in the network, which arises due to several positive feedback loops, and is switched on/off by input environmental signals. The switch stabilizes the expression levels of the three genes, and through their regulatory roles on the downstream target genes, leads to a binary decision: when OCT4, SOX2, and NANOG are expressed and the switch is on, the self-renewal genes are on and the differentiation genes are off. The opposite holds when the switch is off. The model is extremely robust to parameter changes. In addition to providing a self-consistent picture of the transcriptional circuit, the model generates several predictions. Increasing the binding strength of NANOG to OCT4 and SOX2, or increasing its basal transcriptional rate, leads to an irreversible bistable switch: the switch remains on even when the activating signal is removed. Hence, the stem cell can be manipulated to be self-renewing without the requirement of input signals. We also suggest tests that could discriminate between a variety of feedforward regulation architectures of the target genes by OCT4, SOX2, and NANOG.
This model is hosted on BioModels Database
and identified by: MODEL7957942740
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
2024-09-02 | BIOMD0000000204 | BioModels
Project description:Understanding mechanisms of epigenetic regulation in embryonic stem cells (ESCs) is of fundamental importance for stem cell and developmental biology. Here we identify Spic, a member of the ETS family of transcription factors, as a specific marker of ground state pluripotency. We show that Spic is rapidly induced in ESCs cultured with GSK3-, MEK-inhibitors and LIF (2iL), and in response to MEK/ERK inhibition. ChIP-seq analysis demonstrated that Spic binds to enhancer elements that are associated with pluripotency genes. Interaction proteomics and genomic profiling confirmed that SPIC interacts with NANOG and stabilizes its binding to chromatin in 2iL-ESCs. Additional gain of function and loss of function experiments revealed that Spic controls genes involved in one carbon (1C) metabolism, Bhmt, Bhmt2, and Dmgdh, and the flux of SAM-to-SAH in 2iL-ESCs. By maintaining low levels of SAM, Spic controls the level of H3K4me3 and H3R17me2 histone methylation in ground state ESCs. Our data highlight the role of uncharacterized axillary transcription factors that link cellular metabolism to epigenetic regulation in ground state pluripotency.
2025-05-06 | PXD039213 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE30995: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [RNA-Seq] GSE31006: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [ChIP-Seq] GSE31007: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [protein binding microarray] GSE31948: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [AS microarray] Refer to individual Series
2011-09-14 | E-GEOD-30992 | biostudies-arrayexpress