Discovery of NANOG enhancers and their essential roles in self-renewal and differentiation in human embryonic stem cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1194612 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31624305_1.fastq.gz | Fastqsanger.gz | |||
| SRR31624305_2.fastq.gz | Fastqsanger.gz | |||
| SRR31624306_1.fastq.gz | Fastqsanger.gz | |||
| SRR31624306_2.fastq.gz | Fastqsanger.gz | |||
| SRR31624307_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 30 |
Similar Datasets
Project description:Human embryonic stem cells (hESCs) are an important system to study development and regeneration. NANOG is a core regulator in hESCs, but it is transcriptionally regulated is not fully understood. In this study, we report the discovery of two NANOG enhancers from a CRISPR interference enhancer screen in hESCs. These enhancers are essential to hESCs, and deletion of a single copy of either enhancers significantly reduced NANOG expression. In addition, hESCs with heterozygous deletion of either enhancers had compromised self-renewal and increased tendency to differentiate. Interestingly, these two NANOG enhancers are involved in a tandem duplication event, but the duplicated counterparts do not regulate NANOG. This work expands our knowledge of functional enhancers in hESCs, and highlights the sensitivity of the hESC state to the dosage of a core regulator.
2024-12-12 | GSE283612 | GEO
Project description:Understanding the mechanism by which embryonic stem (ES) cells self-renew is critical for the realization of their therapeutic potential. Previously it had been shown that in combination with LIF, Id proteins were sufficient to maintain mouse ES cells in a self-renewing state. Here we investigate the requirement for Id1 in maintaing ES cell self-renewal and blocking differentiation. We find that Id1-/- ES cells have a propensity to differentiate and a decreased capacity to self-renew. Chronic or acute loss of Id1 leads to a down-regulation of Nanog, a critical regulator of self-renewal. In addition, in the absence of Id1, ES cells express elevated levels of Brachyury, a marker of mesendoderm differentiation. We find that loss of both Nanog and Id1 is required for the up-regulation of Brachyury, and Id1 maintains Nanog expression by blocking the expression of Zeb1, a repressor of Nanog transcription. These results identify Id1 as an important factor in the maintenance of ES cell self-renewal and suggest a plausible mechanism for its control of lineage commitment. Wild type and Id1-/- ES cells were grown on gelatin under normal self-renewing conditions (in the presence of serum and LIF).
2011-11-01 | E-GEOD-19144 | biostudies-arrayexpress
Project description:Understanding the mechanism by which embryonic stem (ES) cells self-renew is critical for the realization of their therapeutic potential. Previously it had been shown that in combination with LIF, Id proteins were sufficient to maintain mouse ES cells in a self-renewing state. Here we investigate the requirement for Id1 in maintaing ES cell self-renewal and blocking differentiation. We find that Id1-/- ES cells have a propensity to differentiate and a decreased capacity to self-renew. Chronic or acute loss of Id1 leads to a down-regulation of Nanog, a critical regulator of self-renewal. In addition, in the absence of Id1, ES cells express elevated levels of Brachyury, a marker of mesendoderm differentiation. We find that loss of both Nanog and Id1 is required for the up-regulation of Brachyury, and Id1 maintains Nanog expression by blocking the expression of Zeb1, a repressor of Nanog transcription. These results identify Id1 as an important factor in the maintenance of ES cell self-renewal and suggest a plausible mechanism for its control of lineage commitment.
2011-11-01 | GSE19144 | GEO
Project description:The molecular logic of Nanog-induced self-renewal in mouse embryonic stem cells
| PRJNA487194 | ENA
Project description:Differentiated macrophages can self-renew in tissues and expand long-term in culture, but the gene regulatory mechanisms that accomplish self-renewal in the differentiated state have remained unknown. Here we show that in mice, the transcription factors MafB and c-Maf repress a macrophage-specific enhancer repertoire associated with a gene network controlling self-renewal. Single cell analysis revealed that, in vivo, proliferating resident macrophages can access this network by transient down-regulation of Maf transcription factors. The network also controls embryonic stem cell self-renewal but is associated with distinct embryonic stem cell-specific enhancers. This indicates that distinct lineage-specific enhancer platforms regulate a shared network of genes that control self-renewal potential in both stem and mature cells.
2016-02-03 | GSE75722 | GEO
Project description:Identification of Nanog targets by transcriptomic changes of Nanog induction and depletion, identification of Nanog co-binding logic by ChIP-seq of Nanog co-binding factors with and without Nanog depletion. H3K27me3 with Nanog induction in +/- Lif.
2019-01-14 | GSE118898 | GEO
Project description:The embryonic stem (ES) cell transcriptional and epigenetic networks are critical for the maintenance of ES cell self-renewal. However, it remains unclear whether components of these networks functionally interact and if so, what factors mediate such interactions. Here we show that WD-repeat protein-5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively correlates with the undifferentiated state and is a novel regulator of ES cell self-renewal. We demonstrate that Wdr5, an ‘effector’ of H3K4 methylation, interacts with the pluripotency transcription factor Oct4. In concordance, genome-wide ChIP-Seq and transcriptome analyses demonstrate overlapping gene regulatory functions between Oct4 and Wdr5. We show that the Oct4-Sox2-Nanog circuitry cooperates with trxG for transcriptional activation of key self-renewal regulators. Furthermore, Wdr5 expression is required for the efficient formation of induced pluripotent stem (iPS) cells. Collectively, these findings implicate an integrated model of transcriptional and epigenetic control, mediated by select trxG members, for the maintenance of ES cell self-renewal and somatic cell reprogramming. 7 Samples
2011-04-08 | E-GEOD-22934 | biostudies-arrayexpress
Project description:Cell lines geneticially engineered to undergo conditional asymmetric self-renewal were used to identify genes whose expression is asymmetric self-renewal associated (ASRA). Non-random sister chromatid segregation occurs concordantly with asymmetric self-renewal in these cell lines. Asymmetric self-renewal occurs when murine embryo fibroblasts that are otherwise p53-null are induced to express physiological levels of wildtype p53 protein (Asym). To distinguish p53-responsive genes that also require induction of asymmetric self renewal (i.e., ASRA genes) and/or non-random sister chromatid segregation for change, an additional control cell line, which continues to symmetrically self-renew (with random sister chromatid segregation) even when p53 is induced, was also compared (Symp53). This congenic cell line constitutively expresses the type II inosine monophosphate dehydrogenase (IMPDH II; the rate-limiting enzmye for guanine ribonucleotide biosynthesis) and, thereby, prevents p53-induced asymmetric self-renewal and non-random sister chromatid segregation. Three biological replicates of asymmetrically self-renewing cultures (Asym1-3) were compared with cultures that were symmetrically self-renewing - either because they did not express p53 (3 biological replicates, Sym1-3) or they expressed constitutive IMPDH II (i.e., not regulated by p53) as well as p53 (2 biological replicates, Symp53_1 and 2.)
2010-12-22 | E-GEOD-25334 | biostudies-arrayexpress
Project description:We have used mouse embryonic stem cells (ESCs) as a model to study the signaling mechanisms that regulate self-renewal and commitment to differentiation. We hypothesized that genes critical to stem cell fate would be dynamically regulated at the initiation of commitment. Time course microarray analysis following initiation of commitment led us to propose a model of ESC maintenance in which highly regulated transcription factors and chromatin remodeling genes (down-regulated in our time course) maintain repression of genes responsible for cell differentiation, morphogenesis and development (up-regulated in our time course). Microarrays of Oct4, Nanog and Sox2 shRNA knockdown cell lines confirmed predicted regulation of target genes. shRNA knockdowns of candidate genes were tested in a novel high throughput screen of self-renewal, confirming their role in ESC pluripotency. We have identified genes that are critical for self-renewal and those that initiate commitment and developed draft transcriptional networks that control self-renewal and early development. Keywords: genetic modification Gene expression in Oct4 knockdown, Sox2 knockdown and their empty vector contol ES cells was analyzed.
2010-06-11 | E-GEOD-7520 | biostudies-arrayexpress
Project description:Cell lines geneticially engineered to undergo conditional asymmetric self-renewal were used to identify genes whose expression is asymmetric self-renewal associated (ASRA). Non-random sister chromatid segregation occurs concordantly with asymmetric self-renewal in these cell lines. Asymmetric self-renewal occurs when murine embryo fibroblasts that are otherwise p53-null are induced to express physiological levels of wildtype p53 protein (Asym). To distinguish p53-responsive genes that also require induction of asymmetric self renewal (i.e., ASRA genes) and/or non-random sister chromatid segregation for change, an additional control cell line, which continues to symmetrically self-renew (with random sister chromatid segregation) even when p53 is induced, was also compared (Symp53). This congenic cell line constitutively expresses the type II inosine monophosphate dehydrogenase (IMPDH II; the rate-limiting enzmye for guanine ribonucleotide biosynthesis) and, thereby, prevents p53-induced asymmetric self-renewal and non-random sister chromatid segregation.
2010-12-22 | GSE25334 | GEO