Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE18737
PROVIDER: PRJNA121645 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Single cell-based studies have revealed tremendous cellular heterogeneity in stem cell and progenitor compartments, suggesting continuous differentiation trajectories with intermixing of cells at various states of lineage commitment and notable degree of plasticity during organogenesis. The hepato-pancreato-biliary organ system relies on a small endoderm progenitor compartment that gives rise to a variety of different adult tissues, including liver, pancreas, gallbladder, and extra-hepatic bile ducts. Experimental manipulation of various developmental signals in the mouse embryo underscored important cellular plasticity in this embryonic territory. This is also reflected in the existence of human genetic syndromes as well as congenital or environmentally-caused human malformations featuring multiorgan phenotypes in liver, pancreas and gallbladder. Nevertheless, the precise lineage hierarchy and succession of events leading to the segregation of an endoderm progenitor compartment into hepatic, biliary, and pancreatic structures are not yet established. Here, we combine computational modelling approaches with genetic lineage tracing to assess the tissue dynamics accompanying the ontogeny of the hepato-pancreato-biliary organ system. We show that a multipotent progenitor domain persists at the border between liver and pancreas, even after pancreatic fate is specified, contributing to the formation of several organ derivatives, including the liver. Moreover, using single-cell RNA sequencing we define a specialized niche that possibly supports such extended cell fate plasticity.
2021-07-01 | MODEL2105030001 | BioModels
Project description:Epigenetics helps define current cell states, yet also shapes how cells respond to external cues such as differentiation or stress. The epigenetic plasticity of a cell describes how flexible this regulation is. Bivalent chromatin is an exemplar of epigenetic plasticity. This co-occurrence of the active-associated H3K4me3 and inactive-associated H3K27me3 histone modifications on opposite tails of the same nucleosome was first described in mouse embryonic stem cells where it is found at promoters of key developmental genes. It has been postulated that bivalent chromatin poises these promoters, keeping them free from repressive DNAmethylation, enabling them to be transcriptionally upregulated upon differentiation. Bivalent chromatin has also been reported in other cell types including somatic cells and cancer cells, however we know little of the dynamics, resolution and regulation of this chromatin state. This is partly due to the technical challenges distinguishing bone-fide bivalent chromatin, where both marks are on the same nucleosome, from sample heterogeneity where some alleles have H3K4me3 and others H3K27me3. We developed a robust and sensitive reChIP method to accurately profile bivalent chromatin in as little as 2 million mouse embryonic stem cells. We validated the sensitivity of our method to detect changes in bivalent chromatin by profiling mouse ESCs lacking the epigenetic priming factors Dppa2 and Dppa4.
2024-02-26 | GSE242686 | GEO
Project description:MLL-fusion proteins are potent inducers of cancer in hematopoietic cells, where they are known to cause changes in global gene expression. How MLL-fusion proteins interact with the genome has not been established, so we have limited understanding of the pathway by which these proteins generate aberrant gene expression programs. Here we describe how the MLL-AF4 protein occupies the genome in human leukemia cells and its striking effects on chromatin states. We find that the MLL-AF4 fusion protein selectively occupies regions of the genome that contain developmental regulatory genes important for hematopoietic stem cell identity and self-renewal. These MLL-AF4 bound regions have grossly altered chromatin structure, with histone modifications catalyzed by Trithorax Group (TrxG) proteins and Dot1 extending across unusually large domains. This indicates that a key feature of MLL-associated leukemogenesis is aberrant targeting of chromatin modifiers to regions of the genome controlling hematopoietic development. Our results define the direct targets of the MLL-fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in human cancer. Keywords: cell type comparison This dataset includes expression data for two replicates each of SEM and REH leukemia cell lines and ChIP-chip data targeting RNAP2, H3K4me3, H3K79me2, ENL, AF4-C, and MLL-N in SEM and REH leukemia cell lines.
2008-12-14 | E-GEOD-13313 | biostudies-arrayexpress
Project description:Collombet2016 - Lymphoid and myeloid cell
specification and transdifferentiation
This model is described in the article:
Logical modeling of lymphoid
and myeloid cell specification and transdifferentiation
Samuel Collombet, Chris van Oevelen,
Jose Luis Sardina Ortega, Wassim Abou-Jaoudé, Bruno Di
Stefano, Morgane Thomas-Chollier, Thomas Graf, and Denis
Thieffry
Proceedings of the National Academy of
Sciences of the United States of America
Abstract:
Blood cells are derived from a common set of hematopoietic
stem cells, which differentiate into more specific progenitors
of the myeloid and lymphoid lineages, ultimately leading to
differentiated cells. This developmental process is controlled
by a complex regulatory network involving cytokines and their
receptors, transcription factors, and chromatin remodelers.
Using public data and data from our own molecular genetic
experiments (quantitative PCR, Western blot, EMSA) or
genome-wide assays (RNA-sequencing, ChIP-sequencing), we have
assembled a comprehensive regulatory network encompassing the
main transcription factors and signaling components involved in
myeloid and lymphoid development. Focusing on B-cell and
macrophage development, we defined a qualitative dynamical
model recapitulating cytokine-induced differentiation of common
progenitors, the effect of various reported gene knockdowns,
and the reprogramming of pre-B cells into macrophages induced
by the ectopic expression of specific transcription factors.
The resulting network model can be used as a template for the
integration of new hematopoietic differentiation and
transdifferentiation data to foster our understanding of
lymphoid/myeloid cell-fate decisions.
This model is hosted on
BioModels Database
and identified by:
MODEL1610240000.
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.
2017-06-08 | MODEL1610240000 | BioModels
Project description:MLL-fusion proteins are potent inducers of cancer in hematopoietic cells, where they are known to cause changes in global gene expression. How MLL-fusion proteins interact with the genome has not been established, so we have limited understanding of the pathway by which these proteins generate aberrant gene expression programs. Here we describe how the MLL-AF4 protein occupies the genome in human leukemia cells and its striking effects on chromatin states. We find that the MLL-AF4 fusion protein selectively occupies regions of the genome that contain developmental regulatory genes important for hematopoietic stem cell identity and self-renewal. These MLL-AF4 bound regions have grossly altered chromatin structure, with histone modifications catalyzed by Trithorax Group (TrxG) proteins and Dot1 extending across unusually large domains. This indicates that a key feature of MLL-associated leukemogenesis is aberrant targeting of chromatin modifiers to regions of the genome controlling hematopoietic development. Our results define the direct targets of the MLL-fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in human cancer.
2012-05-31 | GSE38338 | GEO
Project description:MLL-fusion proteins are potent inducers of cancer in hematopoietic cells, where they are known to cause changes in global gene expression. How MLL-fusion proteins interact with the genome has not been established, so we have limited understanding of the pathway by which these proteins generate aberrant gene expression programs. Here we describe how the MLL-AF4 protein occupies the genome in human leukemia cells and its striking effects on chromatin states. We find that the MLL-AF4 fusion protein selectively occupies regions of the genome that contain developmental regulatory genes important for hematopoietic stem cell identity and self-renewal. These MLL-AF4 bound regions have grossly altered chromatin structure, with histone modifications catalyzed by Trithorax Group (TrxG) proteins and Dot1 extending across unusually large domains. This indicates that a key feature of MLL-associated leukemogenesis is aberrant targeting of chromatin modifiers to regions of the genome controlling hematopoietic development. Our results define the direct targets of the MLL-fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in human cancer. This dataset includes expression data for two replicates each of SEM and REH leukemia cell lines, ChIP-chip data targeting RNAP2, H3K4me3, H3K79me2, ENL, AF4-C, and MLL-N in SEM and REH leukemia cell lines, and ChIP-Seq data of H3K79me2, H3K4me3, ans WCE in SEM and REH cell lines. This Series contains the ChIP-Seq data only. The expression and ChIP-chip data are provided in GEO Series GSE13313.
2012-05-31 | E-GEOD-38338 | biostudies-arrayexpress
Project description:The balance between self-renewal and differentiation of hematopoietic stem cells (HSCs) is orchestrated by the combinatorial function of transcription factors and epigenetic regulators. Here, we report that the H4K16 acetyl-transferase MOF regulates chromatin accessibility and hematopoietic gene expression during erythroid commitment. Mof expression is controlled via a transcriptional feedforward pathway involving Runx1 and Gfi1b, which is crucial for the erythroid lineage bias. Single-cell RNA-seq of HSCs revealed that Mof haploinsufficient mice accumulate an otherwise rare HSC subset, indicating impaired differentiation.We propose that an intricate transcription factor network ensures dynamic chromatin targeting by MOF, which defines an essential epigenetic node regulating HSC plasticity, identity and differentiation. We propose that an intricate transcription factor network ensures dynamic chromatin targeting by MOF, which defines an essential epigenetic node regulating HSC plasticity, identity and differentiation. We propose that an intricate transcription factor network ensures dynamic chromatin targeting by MOF, which defines an essential epigenetic node regulating HSC plasticity, identity and differentiation. We propose that an intricate transcription factor network ensures dynamic chromatin targeting by MOF, which defines an essential epigenetic node regulating HSC plasticity, identity and differentiation.
2020-03-13 | GSE118194 | GEO
Project description:The balance between self-renewal and differentiation of hematopoietic stem cells (HSCs) is orchestrated by the combinatorial function of transcription factors and epigenetic regulators. Here, we report that the H4K16 acetyl-transferase MOF regulates chromatin accessibility and hematopoietic gene expression during erythroid commitment. Mof expression is controlled via a transcriptional feedforward pathway involving Runx1 and Gfi1b, which is crucial for the erythroid lineage bias. Single-cell RNA-seq of HSCs revealed that Mof haploinsufficient mice accumulate an otherwise rare HSC subset, indicating impaired differentiation.We propose that an intricate transcription factor network ensures dynamic chromatin targeting by MOF, which defines an essential epigenetic node regulating HSC plasticity, identity and differentiation. We propose that an intricate transcription factor network ensures dynamic chromatin targeting by MOF, which defines an essential epigenetic node regulating HSC plasticity, identity and differentiation. We propose that an intricate transcription factor network ensures dynamic chromatin targeting by MOF, which defines an essential epigenetic node regulating HSC plasticity, identity and differentiation. We propose that an intricate transcription factor network ensures dynamic chromatin targeting by MOF, which defines an essential epigenetic node regulating HSC plasticity, identity and differentiation.
2020-03-13 | GSE118192 | GEO
Project description:Bivalent chromatin refers to the simultaneous occurrence of transcription activation (H3K4me3)- and repression (H3K27me3)-associated histone modifications at gene promoters. This mark was first identified in ES cells and proposed to maintain genes in a poised state for future resolution to fully-active (H3K4me3-only) or fully-repressed (H3K27me3-only) states. In this report we rigorously test the poising hypothesis using a well-established developmental paradigm of hematopoietic stem cell differentiation to T lymphoid lineage committed cells. We show that bivalent chromatin is generated and resolved at specific stages of hematopoiesis. The epigenetic states from which it is generated and the states to which it is resolved vary with developmental stage, suggesting that bivalency serves different functions at each stage. Moreover, singly-marked genes do not transition to the opposing univalent state via a bivalent intermediate.
2018-12-31 | GSE43428 | GEO
Project description:MLL-fusion proteins are potent inducers of cancer in hematopoietic cells, where they are known to cause changes in global gene expression. How MLL-fusion proteins interact with the genome has not been established, so we have limited understanding of the pathway by which these proteins generate aberrant gene expression programs. Here we describe how the MLL-AF4 protein occupies the genome in human leukemia cells and its striking effects on chromatin states. We find that the MLL-AF4 fusion protein selectively occupies regions of the genome that contain developmental regulatory genes important for hematopoietic stem cell identity and self-renewal. These MLL-AF4 bound regions have grossly altered chromatin structure, with histone modifications catalyzed by Trithorax Group (TrxG) proteins and Dot1 extending across unusually large domains. This indicates that a key feature of MLL-associated leukemogenesis is aberrant targeting of chromatin modifiers to regions of the genome controlling hematopoietic development. Our results define the direct targets of the MLL-fusion protein, reveal the global role of epigenetic misregulation in leukemia, and identify new targets for therapeutic intervention in human cancer. Keywords: cell type comparison
2008-12-15 | GSE13313 | GEO