Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA302853 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Genome-Wide Chromatin Landscape Transitions Identify Novel Pathways in Early Commitment to Osteoblast Differentiation (microarray)
| PRJNA302852 | ENA
Project description:The life cycle of Trypanosoma brucei involves several cell differentiation transitions that allow transmission, survival and proliferation of these parasites. One of these transitions, the differentiation of growth-arrested stumpy forms in the mammalian blood into proliferating insect-stage procyclic forms, can be induced synchronously in vitro by addition of cis-aconitate (CA). Using single-cell analysis by flow-cytometry to follow differentiation, we show that this transition is an irreversible bistable switch where cells commit to differentiation after 1-3 hours of exposure to CA. This irreversibility implies the existence of positive feedback mechanisms that allow commitment to differentiation: i.e. the establishment of “memory” of exposure to the differentiation signal. Such mechanisms probably depend on post-translational modifications (e.g. phosphorylation) and/or synthesis of regulatory proteins. Using the reversible protein synthesis inhibitor cycloheximide, we find that protein synthesis is required for establishment of signal memory and normal commitment to differentiation. To characterize the ‘commitment proteome’, we performed SILAC phosphoproteomics to provide a detailed map of the protein expression and phosphorylation events during the early stages of differentiation in a synchronised parasite population. Using a rigorous candidate gene approach we have also demonstrated that the stumpy form enriched serine-throenine protein kinases TbNRKA/B stringently control the earliest events in differentiation identifying these kinases as major regulators of trypanosome development.
2018-05-08 | PXD002165 | Pride
Project description:Lineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. We performed dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) along ex vivo human erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis uncovers differential fate commitment dynamics between the two lineages as they exit the stem and progenitor stage. Collectively, these data provide novel insights into the global regulatory landscape during hematopoiesis.
2021-09-30 | GSE182816 | GEO
Project description:Lineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. We performed dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) along ex vivo human erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis uncovers differential fate commitment dynamics between the two lineages as they exit the stem and progenitor stage. Collectively, these data provide novel insights into the global regulatory landscape during hematopoiesis.
2021-09-30 | GSE183267 | GEO
Project description:Lineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. We performed dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) along ex vivo human erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis uncovers differential fate commitment dynamics between the two lineages as they exit the stem and progenitor stage. Collectively, these data provide novel insights into the global regulatory landscape during hematopoiesis.
2021-09-30 | GSE183266 | GEO
Project description:Lineage commitment and differentiation is driven by the concerted action of master transcriptional regulators at their target chromatin sites. Multiple efforts have characterized the key transcription factors (TFs) that determine the various hematopoietic lineages. However, the temporal interactions between individual TFs and their chromatin targets during differentiation and how these interactions dictate lineage commitment remains poorly understood. We performed dense, daily, temporal profiling of chromatin accessibility (DNase I-seq) and gene expression changes (total RNA-seq) along ex vivo human erythropoiesis to comprehensively define developmentally regulated DNase I hypersensitive sites (DHSs) and transcripts. We link both distal DHSs to their target gene promoters and individual TFs to their target DHSs, revealing that the regulatory landscape is organized in distinct sequential regulatory modules that regulate lineage restriction and maturation. Finally, direct comparison of transcriptional dynamics (bulk and single-cell) and lineage potential between erythropoiesis and megakaryopoiesis uncovers differential fate commitment dynamics between the two lineages as they exit the stem and progenitor stage. Collectively, these data provide novel insights into the global regulatory landscape during hematopoiesis.
2021-09-30 | GSE183268 | GEO
Project description:We describe here a novel role for CHD1 in regulating the osteoblast cell fate by studying the effect of CHD1 depletion on the epigenetic landscape and on mRNA expression in mesenchymal stem cells (MSC) (Simonsen et al. 2012) and fetal Osteoblast (hFOB 1.19) (Harris et al. 1995) during osteoblast differentiation.
2017-09-03 | GSE89179 | GEO
Project description:Bone marrow-derived mesenchymal stem cells (MSCs) differentiate into osteoblasts upon induction by signals present in their niche. As the global signaling cascades involved in the early phases of MSCs osteoblast (OB) differentiation are not well-defined, we employed quantitative mass spectrometry (SILAC based) to delineate changes in human MSCs proteome and phosphoproteome during the first 24 hours of their OB lineage commitment. The temporal profiles of 6,252 proteins and 15,059 phosphorylation sites suggested at least two distinct signaling waves: one peaking within 30 to 60 min after induction and a second upsurge after 24 hours
2021-09-08 | PXD011001 | Pride
Project description:Differentiation of multipotent mesenchymal stem cells into bone-forming osteoblasts requires strict coordination of transcriptional pathways. Aryl hydrocarbon receptor (AhR) ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), have been shown to alter osteoblast differentiation in vitro and bone formation in multiple developmental in vivo models. The goal of the present study was to establish a global transcriptomic landscape during early, intermediate, and apical stages of osteogenic differentiation in vitro in response to TCDD exposure. Human bone-derived mesenchymal stem cells (hBMSC) were cultured in growth media (GM), osteogenic differentiation media (ODM), or osteogenic differentiation media containing 10 nM TCDD (ODM+TCDD), thus enabling a comparison of the transcriptomic profiles of undifferentiated, differentiated, and differentiated -TCDD-exposed hBMSCs, respectively. In this test system, exposure to TCDD attenuated differentiation of hBMSCs into osteoblasts as evidenced by reduced alkaline phosphatase activity and mineralization. At various timepoints, we observed altered expression of genes that play a role in the Wnt, FGF, BMP/TGF-β developmental pathways, as well as pathways related to extracellular matrix organization and deposition. Reconstruction of gene regulatory networks with the iDREM analysis revealed modulation of transcription factors (TF) including POLR3G, NR4A1, RDBP, GTF2B, POU2F2 and ZEB1, which may putatively influence osteoblast differentiation and the requisite deposition and mineralization of bone extracellular matrix. We demonstrate that the combination of RNA-Seq data in conjunction with the iDREM regulatory model, captures the transcriptional dynamics underlying mesenchymal stem cell differentiation under different conditions in vitro. Model predictions are consistent with existing knowledge and provides a new tool to identify novel pathways and transcription factors that may facilitate a better understanding of the osteoblast differentiation process, perturbation by exogenous agents, and potential intervention strategies targeting those specific pathways.
2023-02-08 | GSE217334 | GEO