Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA291545 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Identification of global regulators of T-helper cell lineage specification (microarray)
| PRJNA291543 | ENA
Project description:Identification of global regulators of T-helper cell lineage specification (RNA-Seq)
| PRJNA291702 | ENA
Project description:Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell enriched and -depleted mouse intestinal organoids to obtain a holistic view of the molecular mechanisms that drive differential gene expression during adult intestinal stem cell differentiation. Our data revealed a global rewiring of the transcriptome and proteome between intestinal stem cells and enterocytes, with the majority of dynamic protein expression being transcription-driven. Integrating absolute mRNA and protein copy numbers revealed post-transcriptional regulation of gene expression. Probing the epigenetic landscape identified a large number of cell-type specific regulatory elements, which revealed Hnf4g as a major driver of enterocyte differentiation. In summary, by applying an integrative systems biology approach we uncovered multiple layers of gene expression regulation, which contribute to lineage specification and plasticity of the mouse small intestinal epithelium.
2018-06-25 | PXD009700 | Pride
Project description:The integration of cell metabolism with signalling pathways, transcription factor networks and epigenetic mediators is critical in coordinating molecular and cellular events during embryogenesis. Induced pluripotent stem cells (IPSCs) are an established model for embryogenesis, germ layer specification and cell lineage differentiation, advancing the study of human embryonic development and the translation of innovations in drug discovery, disease modelling and cell-based therapies. The metabolic regulation of IPSC pluripotency is mediated by balancing glycolysis and oxidative phosphorylation, but there is a paucity of data regarding the influence of individual metabolite changes during cell lineage differentiation. We used <sup>1</sup>H NMR metabolite fingerprinting and footprinting to monitor metabolite levels as IPSCs are directed in a three-stage protocol through primitive streak/mesendoderm, mesoderm and chondrogenic populations. Metabolite changes were associated with central metabolism, with aerobic glycolysis predominant in IPSC, elevated oxidative phosphorylation during differentiation and fatty acid oxidation and ketone body use in chondrogenic cells. Metabolites were also implicated in the epigenetic regulation of pluripotency, cell signalling and biosynthetic pathways. Our results show that <sup>1</sup>H NMR metabolomics is an effective tool for monitoring metabolite changes during the differentiation of pluripotent cells with implications on optimising media and environmental parameters for the study of embryogenesis and translational applications.
2023-05-24 | MTBLS4854 | MetaboLights
Project description:Alternative splicing is critical for development. However, its role in the specification of the three embryonic germ layers is poorly understood. By performing RNA-Seq on human embryonic stem cells (hESCs) and derived endoderm, cardiac mesoderm, and ectoderm cell lineages, we detect distinct alternative splicing programs associated with each lineage. The most prominent splicing program differences are observed between definitive endoderm and cardiac mesoderm. Integrative multi-omics analyses link each program with lineage-specific RNA binding protein regulators, and further suggest a widespread role for Quaking (QKI) in the specification of cardiac mesoderm. Remarkably, knockout of QKI disrupts the cardiac mesoderm-associated alternative splicing program and formation of myocytes. These changes likely arise in part through reduced expression of BIN1 splice variants linked to cardiac development. Collectively, our results thus uncover alternative splicing programs associated with the three germ lineages and demonstrate an important role for QKI in the formation of cardiac mesoderm.
2022-02-01 | MSV000088762 | MassIVE
Project description:deBack2012 - Lineage Specification in Pancreas Development
This model of two neighbouring pancreas precursor cells, describes the exocrine versus endocrine lineage specification process. To account for the tissue scale patterns, this couplet model has been extended to hundreds of coupled cells.
This model is described in the article:
On the role of lateral stabilization during early patterning in the pancreas
de Back W., Zhou JX, Brusch L
J. R. Soc. Interface 6 February 2013 vol. 10 no. 79 20120766
Abstract:
The cell fate decision of multi-potent pancreatic progenitor cells between the exocrine and endocrine lineages is regulated by Notch signalling, mediated by cell–cell interactions. However, canonical models of Notch-mediated lateral inhibition cannot explain the scattered spatial distribution of endocrine cells and the cell-type ratio in the developing pancreas. Based on evidence from acinar-to-islet cell transdifferentiation in vitro, we propose that lateral stabilization, i.e. positive feedback between adjacent progenitor cells, acts in parallel with lateral inhibition to regulate pattern formation in the pancreas. A simple mathematical model of transcriptional regulation and cell–cell interaction reveals the existence of multi-stability of spatial patterns whose simultaneous occurrence causes scattering of endocrine cells in the presence of noise. The scattering pattern allows for control of the endocrine-to-exocrine cell-type ratio by modulation of lateral stabilization strength. These theoretical results suggest a previously unrecognized role for lateral stabilization in lineage specification, spatial patterning and cell-type ratio control in organ development.
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2024-09-02 | BIOMD0000000435 | BioModels
Project description:The stepwise conversion of multipotent precursors into committed T-cell progenitors depends on several transcriptional regulators, but the interplay between these factors is still obscure. This is particularly true in human since the core early Notch signalling pathway also supports NK cell development and requires tight regulation for efficient T-lineage commitment and differentiation. Here, we show that GATA3, in contrast to TCF1, induces T-lineage commitment following NOTCH1-induced T-lineage specification through direct regulation of at least 3 distinct processes: repression of NK-cell fate, activation of T-lineage genes to promote further differentiation, and downmodulation of Notch signalling activity. GATA3-mediated repression of the NOTCH1 target gene DTX1 hereby is essential to induce T-lineage commitment at the expense of NK cell differentiation. Thus, human T-lineage commitment is dependent on the precise collaboration of several transcriptional regulators that integrate through both positive and negative regulatory loops. ChIP-sequencing data was generated for GATA3 in human thymocytes
2016-04-06 | E-GEOD-71751 | biostudies-arrayexpress
Project description:Although higher-order genome organization is tissue-specific, its functional relevance and mechanistic basis are poorly understood. Here we analyzed the dynamics of chromatin interactions for lineage-specific cytokine loci during T helper (Th) differentiation. The naive-to-effector transition is accompanied by a profound shift from promiscuous to highly selective and functionally enriched genome-wide contacts. Despite the establishment of divergent interactomes and global reprogramming of transcription in Th1 versus Th2 commitment, the overall expression status of the contact genes is surprisingly similar between the two lineages. Importantly, the genomic contacts are retained and strengthened precisely at DNA binding sites of the specific lineage-determining STAT transcription factor. The global aggregation of STAT binding loci from genic and non-genic regions highlights a new role for differentiation-promoting transcription factors in direct specification of higher-order nuclear architecture through interacting with regulatory regions. Such subnuclear environments have implications for efficient functioning of the mature effector lymphocytes. Nineteen arrays total: Eighteen microarrays from individual biological replicates, one microarray from a pool of two biological replicates.
2012-12-03 | E-GEOD-38717 | biostudies-arrayexpress