Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA138883 | ENA |
REPOSITORIES: ENA
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Project description:Raw .d files containing LC-DTIMS-CID-MS for the analysis of lipidomic changes during stem cell differentiation into mesodermal and neural cell lineages.
2024-11-22 | MSV000096506 | GNPS
Project description:<p>During development of the human brain, multiple cell types with diverse regional identities are generated. Here we report a system to generate early human brain forebrain and mid/hindbrain cell types from human embryonic stem cells (hESCs), and infer and experimentally confirm a lineage tree for the generation of these types based on single-cell RNA-Seq analysis. We engineered <i>SOX2<sup>Cit/+</sup></i> and <i>DCX<sup>Cit/Y</sup></i> hESC lines to target progenitors and neurons throughout neural differentiation for single-cell transcriptomic profiling, then identified discrete cell types consisting of both rostral (cortical) and caudal (mid/hindbrain) identities. Direct comparison of the cell types were made to primary tissues using gene expression atlases and fetal human brain single-cell gene expression data, and this established that the cell types resembled early human brain cell types, including preplate cells. From the single-cell transcriptomic data a Bayesian algorithm generated a unified lineage tree, and predicted novel regulatory transcription factors. The lineage tree highlighted a prominent bifurcation between cortical and mid/hindbrain cell types, confirmed by clonal analysis experiments. We demonstrated that cell types from either branch could preferentially be generated by manipulation of the canonical Wnt/beta-catenin pathway. In summary, we present an experimentally validated lineage tree that encompasses multiple brain regions, and our work sheds light on the molecular regulation of region-specific neural lineages during human brain development.</p>
| phs001205 | dbGaP
Project description:Dynamic transcriptomes during neural differentiation of human embryonic stem cells
| PRJNA125337 | ENA
Project description:Defining molecular controls that orchestrate human brain development is essential for uncovering the complexity behind neurodevelopment and the pathogenesis of neurological disorders. Due to the difficulties in accessing embryonic and fetal brain tissues, the differentiation of human pluripotent stem cell (hPSC)-derived three-dimensional neural organoids has made it possible to recapitulate this developmental process in vitro and provide a unique opportunity to investigate human brain development and disease. To elucidate the molecular programs that drive this highly dynamic process, here, we generate a comprehensive trans-omic map of the phosphoproteome, proteome, and transcriptome of the initial stages of pluripotency and neural differentiation towards the formation of cerebral organoids. Our integrative analysis uncovers key phospho-signalling events underlying neural lineage differentiation, and their convergence on transcriptional (co-)factors and chromatin remodellers that govern downstream gene regulatory networks (GRNs). Comparative analysis with developing human and mouse embryos using these GRNs demonstrates the fidelity of our early cerebral organoids in modelling embryonic brain development. Finally, we demonstrate biochemical modulation of the AKT signalling as a key molecular switch for controlling human cerebral organoid formation. Our data provides a comprehensive resource to gain insight into the molecular controls in human embryonic brain development and also provide a guide for future development of protocols for human cerebral organoid differentiation.
2024-04-23 | PXD047423 | Pride
Project description:Chavez2009 - a core regulatory network of OCT4 in human embryonic stem cells
A core OCT4-regulated network has been identified as a test case, to analyase stem cell characteristics and cellular differentiation.
This model is described in the article:
In silico identification of a core regulatory network of OCT4 in human embryonic stem cells using an integrated approach.
Chavez L, Bais AS, Vingron M, Lehrach H, Adjaye J, Herwig R
BMC Genomics, 2009, 10:314
Abstract:
BACKGROUND: The transcription factor OCT4 is highly expressed in pluripotent embryonic stem cells which are derived from the inner cell mass of mammalian blastocysts. Pluripotency and self renewal are controlled by a transcription regulatory network governed by the transcription factors OCT4, SOX2 and NANOG. Recent studies on reprogramming somatic cells to induced pluripotent stem cells highlight OCT4 as a key regulator of pluripotency.
RESULTS: We have carried out an integrated analysis of high-throughput data (ChIP-on-chip and RNAi experiments along with promoter sequence analysis of putative target genes) and identified a core OCT4 regulatory network in human embryonic stem cells consisting of 33 target genes. Enrichment analysis with these target genes revealed that this integrative analysis increases the functional information content by factors of 1.3 - 4.7 compared to the individual studies. In order to identify potential regulatory co-factors of OCT4, we performed a de novo motif analysis. In addition to known validated OCT4 motifs we obtained binding sites similar to motifs recognized by further regulators of pluripotency and development; e.g. the heterodimer of the transcription factors C-MYC and MAX, a prerequisite for C-MYC transcriptional activity that leads to cell growth and proliferation.
CONCLUSION: Our analysis shows how heterogeneous functional information can be integrated in order to reconstruct gene regulatory networks. As a test case we identified a core OCT4-regulated network that is important for the analysis of stem cell characteristics and cellular differentiation. Functional information is largely enriched using different experimental results. The de novo motif discovery identified well-known regulators closely connected to the OCT4 network as well as potential new regulators of pluripotency and differentiation. These results provide the basis for further targeted functional studies.
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2005-01-01 | MODEL1305010000 | BioModels
Project description:One of the promising approaches to slow down or treat neurodegenerative diseases or spinal cord injuries represent cell therapies. The grafted cells could either integrate into the damaged tissue to replace dead or damaged cells or by secretion of different factors modulate inflammatory reaction, reduce tissue damage and support neuronal survival. However, due to the heterogeneity of in vitro cultured cells, comprehensive characterization of such cells is absolutely crucial to prevent safety risks.
Here, we performed SWATH-MS analysis to characterize changes in proteome of human neural stem cells (NSCs) during their differentiation either spontaneously by withdrawal of EGF and FGF2 in cell culture media or by trophic support of BDNF/GDNF growth factors. We quantified about 2800 proteins over the 28 days of differentiation and showed that changes in cellular proteomes are caused mostly by differentiation time course, rather than type of differentiation itself and that the major changes in protein expression occurred between day 0 and day 7 of both differentiations.
2021-01-07 | PXD021860 | panorama
Project description:While the core subunits of Polycomb group (PcG) complexes are well characterized, little is known about the dynamics of these protein complexes during cellular differentiation. We used quantitative interaction proteomics to study PcG proteins in mouse embryonic stem cells (mESCs) and neural progenitor cells (NPCs). We found the stoichiometry of PRC1 and PRC2 to be highly dynamic during neural differentiation.
2016-05-19 | PXD003758 | Pride
Project description:We have showed that cancer cells (or tumorigenic cells) resemble neural stem/progenitor cells in regulatory network, tumorigenicity and differentiation potential. We have shown PRMT1 is a protein that is upreguated in and promotes vaious cancers. The expression of its gene is localized to embryonic neural cells during vertebrate embryogenesis. The project is to identify the interaction partners of PRMT1, by which PRMT1 regulates neural stemness in both cancer cells and neural stem cells.
2021-12-20 | PXD026851 | Pride
Project description:Sex-biased Gene Expression During Neural Differentiation of Human Embryonic Stem Cells
| PRJNA1047064 | ENA