Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE19169
PROVIDER: PRJNA120579 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:γH2A.X Modulates Self-renewal and Differentiation of Human Pluripotent Stem Cells.
| PRJNA358227 | ENA
Project description:Pluripotent stem cells are defined by their self-renewal capacity, which is the ability of the stem cells to proliferate indefinitely while maintaining the pluripotent identity essential for their ability to differentiate into any somatic cell lineage. However, understanding the mechanisms that control stem cell fitness versus the pluripotent cell identity is challenging. To investigate the interplay between these two aspects of pluripotency, we performed four parallel genome-scale CRISPR-Cas9 loss-of-function screens interrogating stem cell fitness in hPSC self-renewal conditions, and the dissolution of the primed pluripotency identity during early differentiation. Comparative analyses led to the discovery of genes with distinct roles in pluripotency regulation, including mitochondrial and metabolism regulators crucial for stem cell fitness, and chromatin regulators that control pluripotent identity during early differentiation. We further discovered a core set of factors that control both stem cell fitness and pluripotent identity, including a network of chromatin factors that safeguard pluripotency. Our unbiased and systematic screening and comparative analyses disentangle two interconnected aspects of pluripotency, provide rich datasets for exploring pluripotent cell identity versus cell fitness, and offer a valuable model for categorizing gene function in broad biological contexts.
2024-09-05 | PXD055592 | Pride
Project description:γH2A.X Modulates Self-renewal and Differentiation of Human Pluripotent Stem Cells. [HuGene-2_0-st]
| PRJNA358234 | ENA
Project description:γH2A.X Modulates Self-renewal and Differentiation of Human Pluripotent Stem Cells. [HuGene-1_0-st]
| PRJNA358235 | ENA
Project description:Polycomb group (PcG) proteins are highly conserved epigenetic transcriptional repressors important for the control of numerous developmental gene expression programs and have recently been implicated in the modulation of embryonic stem cell (ESC) identity. We identified the PcG protein PCL2 (polycomb-like 2) in a genome-wide screen for novel regulators of self-renewal and pluripotency and predicted that it would play an important role in mouse ESC fate determination. Using multiple biochemical strategies, we provide evidence that PCL2 is a novel Polycomb Repressive Complex 2 (PRC2)-associated protein in mouse ESCs. Knockdown of Pcl2 in ESCs resulted in heightened self-renewal characteristics, defects in differentiation and altered patterns of histone methylation. Through integration of global gene expression and promoter occupancy analyses of both PCL2 and PRC2 components EZH2 and SUZ12, we have predicted PCL2 target genes and formulated regulatory networks describing the role of PCL2 both in modulating transcription of ESC self-renewal genes in undifferentiated ESCs as well as developmental regulators during early commitment and differentiation. Cells were stably expressing Pcl2 shRNA or shRNA mismatch control sequences. Hybridizations of three biological replicates for both the control and Pcl2 shRNA clone were performed.
2010-02-22 | E-GEOD-16364 | biostudies-arrayexpress
Project description:MTD project_description Inflammation and decreased stem cell function characterize organism aging, yet the relationship between these factors remains incompletely understood. This study shows that aged hematopoietic stem and progenitor cells exhibit increased ground-stage NF-κB activity, which enhances their responsiveness to undergo differentiation and loss of self-renewal in response to inflammation. The study identifies Rad21/cohesin as a critical mediator of NF-κB signals, by increasing chromatin accessibility of inter-/intra-genic and enhancer regions. Rad21/NF-κB are required for normal differentiation, but limit self-renewal of hematopoietic stem cells (HSCs) during aging and inflammation in an NF-κB dependent manner. HSCs from aged mice fail to downregulate Rad21/cohesin and inflammation/differentiation inducing signals in the resolution phase after acute inflammation. and The inhibition of cohesin/NF-κB is sufficient to revert the hypersensitivity of aged HSPCs to inflammation-induced differentiation. During aging, myeloid-biased HSCs with disrupted and naturally occurring reduced expression of Rad21/cohesin are increasingly selected over lymphoid-biased HSCs. Together, Rad21/cohesin mediated NF-κB signaling limits HSPC function during aging and selects for cohesin deficient HSCs with myeloid skewed differentiation.
2018-11-28 | PXD011537 | Pride
Project description:The transition between quiescence and activation in neural stem and progenitor cells (NSPCs) is coupled to reversible changes in energy metabolism with key implications for life-long NSPC self-renewal and neurogenesis. How this metabolic plasticity is ensured between NSPC activity states is unclear. We find that a state-specific rewiring of the mitochondrial proteome by the i-AAA peptidase YME1L is required to preserve NSPC self-renewal. YME1L controls the abundance of numerous mitochondrial substrates in quiescent NSPCs, and its deletion activates a differentiation program characterized by broad metabolic changes causing the irreversible shift away from a fatty acid oxidation-dependent state. Conditional Yme1l deletion in adult NSPCs in vivo results in defective self-renewal and premature differentiation, ultimately leading to NSPC pool depletion. Our results disclose an important role for YME1L in coordinating the switch between metabolic states of NSPCs and suggest that NSPC fate is regulated by compartmentalized changes in protein network dynamics.
2022-02-10 | PXD030995 | Pride
Project description:Chromatin modifiers affect the spatiotemporal expression of gene expression programs that underlie organismal development. The Polycomb repressive complex 2 (PRC2) has emerged as a crucial player in executing neurodevelopmental programs. Here we show that the nucleic acid–binding protein Ybx1 interacts with PRC2 in human and mouse neural progenitor cells (NPCs). During early neural development in vivo, Ybx1 is required for forebrain specification and modulates mid/hindbrain growth. In NPCs, Ybx1 controls the self-renewal and neuronal differentiation. Mechanistically, Ybx1 binds PRC2 gene targets, reduces the levels of PRC2-mediated H3K27me3, and promotes the expression of genes in forebrain specification, cell proliferation, or neuronal differentiation. In Ybx1-knockout NPCs, H3K27me3 reduction by PRC2 enzymatic inhibitor or genetic depletion partially rescues the control of gene expression, self-renewal, and neuronal differentiation. Our findings suggest that Ybx1 modulates H3K27me3 by PRC2 to regulate spatiotemporal gene expression in embryonic neural development and uncover a crucial epigenetic mechanism balancing forebrain–hindbrain lineages and selfrenewal-differentiation choices in NPCs.
2020-06-16 | GSE137783 | GEO
Project description:Chromatin modifiers affect the spatiotemporal expression of gene expression programs that underlie organismal development. The Polycomb repressive complex 2 (PRC2) has emerged as a crucial player in executing neurodevelopmental programs. Here we show that the nucleic acid–binding protein Ybx1 interacts with PRC2 in human and mouse neural progenitor cells (NPCs). During early neural development in vivo, Ybx1 is required for forebrain specification and modulates mid/hindbrain growth. In NPCs, Ybx1 controls the self-renewal and neuronal differentiation. Mechanistically, Ybx1 binds PRC2 gene targets, reduces the levels of PRC2-mediated H3K27me3, and promotes the expression of genes in forebrain specification, cell proliferation, or neuronal differentiation. In Ybx1-knockout NPCs, H3K27me3 reduction by PRC2 enzymatic inhibitor or genetic depletion partially rescues the control of gene expression, self-renewal, and neuronal differentiation. Our findings suggest that Ybx1 modulates H3K27me3 by PRC2 to regulate spatiotemporal gene expression in embryonic neural development and uncover a crucial epigenetic mechanism balancing forebrain–hindbrain lineages and selfrenewal-differentiation choices in NPCs.
2020-06-16 | GSE137778 | GEO
Project description:Polycomb Cbx orthologs mediate the balance between Hematopoietic Stem Cell self-renewal and differentiation
| PRJNA153665 | ENA