Ddo epialleles in neural cells
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ABSTRACT:
PROVIDER: PRJEB16320 | ENA |
REPOSITORIES: ENA
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Project description:Stem cells need to balance self-renewal and differentiation for correct tissue development and homeostasis. Defects in this balance can lead to developmental defects or tumor formation. In recent years, mRNA splicing has emerged as one important mechanism regulating cell fate decisions. Here we address the role of the evolutionary conserved splicing co-factor Barricade (Barc)/CUS2/Tat-SF1 in Drosophila neural stem cell (neuroblast) lineage formation. We show that Barc is required for the generation of neurons during Drosophila brain development by ensuring correct neural progenitor proliferation and differentiation. Barc associates with components of the U2 small nuclear ribonucleic proteins (snRNP), and its depletion causes alternative splicing in form of intron retention in a subset of genes. Using bioinformatics analysis and a cell culture based splicing assay, we found that Barc dependent introns share three major traits: they are short, GC rich and have weak 3’ splice sites. Our results show that Barc, together with the U2snRNP, plays an important role in regulating neural stem cell lineage progression during brain development and facilitates correct splicing of a subset of introns.
2017-11-02 | PXD006068 | Pride
Project description:Wt1 regulates proliferation and differentiation of neural progenitors during brain development
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Project description:Pd1 regulates proliferation and differentiation of neural progenitors during brain development
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Project description:The general area of research interests of my lab is the glycobiology of HSPGs in cell-cell/cell-matrix interactions and growth factor signalling. Heparan sulfate binding proteins in neural development and differentiation. We used the Glyco-gene Chips to study the gene expression responses of mouse neural cells to heparin-binding growth factors. The experimental systems studied is in vivo (developing mouse brain). The goal is to examine the global responses of neural cells to particular growth factors during differentiation in terms of effects on HS biosynthetic enzymes and proteoglycan core proteins, as well as growth factors and their receptors. Analysis of A) P1 mouse brain wild type for Heparan sulfate 2-O sulfotransferase (HS2ST) and B) heterozygous for Heparan sulfate 2-O sulfotransferase (HS2ST) loss of function mutation.
2010-12-11 | E-GEOD-26010 | biostudies-arrayexpress
Project description:Genetic loci displaying environmentally responsive epigenetic marks, termed metastable epialleles, offer a solution to the paradox presented by genetically identical yet phenotypically distinct individuals. The murine viable yellow agouti (Avy) locus is a well-described metastable epiallele that serves as a visual epigenetic biosensor. The Avy locus exhibits a high R-value or ratio of inter-individual (Vi) to inter-tissue (Vt) variance in gene expression, characteristic of what we term the ‘Agouti Expression Fingerprint.’ We propose a novel method for identification of candidate metastable epialleles based on the Agouti Expression Fingerprint, defining candidates as loci with R-values greater than 1.5 on expression microarray. Using Expression data from tissues of the three germ layers (liver, kidney, brain), high variance in agouti RNA levels among isogenic animals coupled with low variance among tissue types in individual animals is demonstrated. Here, we provide proof of concept for the ‘Agouti Expression Fingerprint’; the characterization of epigenetically labile loci in humans will be crucial to the development of novel screening and therapeutic targets for human disease prevention. For expression microarray studies, total RNA was isolated from liver, kidney, and brain tissue from 10 male Avy/a mice (2 per each of the 5 coat color classes) at time of weaning and coat color determination (day 22). Using Affymetrix GeneChip Mouse Genome 2.0 arrays (Santa Clara, CA), we queried the entire mouse genome for candidate metastable epialleles that display the Agouti Fingerprint. Approximately 100 of the greater than 40,000 transcripts on the mouse array displayed an expression pattern characterized as high inter-individual variation coupled with low inter-tissue variation (R-value > 1.5).
2011-07-14 | E-GEOD-28559 | biostudies-arrayexpress
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>
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Project description:Global gene expression profile of midbrain neural differentiation of mESCs from WT and ERb knockout mice, with or without the selective ERb agonist LY3201 (0.5 nM). Estrogen receptor beta (ERβ) is highly expressed in the fetal brain and is essential for proper corticogenesis during development. Nevertheless, the transcriptional signatures regulated by ERβ during defined neural differentiation stages have not been investigated. In the present study we used mouse embryonic stem cells (mESCs) from wildtype (WT) and ERβ knockout (BERKO) mice to derive neural precursor cells (NPCs) and further differentiated these towards defined midbrain neural fates. This allowed us to systematically investigate transcriptionally active determinants during stages of midbrain neurogenesis. We found that ERβ is important during early neural development in regulating proliferation and maintaining the stem cell pool of neuroepithelial and midbrain stem cells. Detailed gene profiling analysis revealed that loss of ERβ perturbs normal neurogenesis by affecting the expression of factors involved in cell adhesion, axon guidance, and signaling of Notch, Wnt, glutamate- and GABA receptors. Among these we identified several factors that are crucial for dopaminergic neuron development and maintenance, as well as the promotion of oligodendrocyte differentiation. We also demonstrate that these effects are largely independent of ligand activated ERβ. Our data identifies ERβ as an important component in midbrain neurogenesis, where its disruption results in premature depletion of the neural stem cell pool in favor of oligodendrogliogenesis.
2017-10-09 | GSE103312 | GEO
Project description:The general area of research interests of my lab is the glycobiology of HSPGs in cell-cell/cell-matrix interactions and growth factor signalling. Heparan sulfate binding proteins in neural development and differentiation. We used the Glyco-gene Chips to study the gene expression responses of mouse neural cells to heparin-binding growth factors. The experimental systems studied is in vivo (developing mouse brain). The goal is to examine the global responses of neural cells to particular growth factors during differentiation in terms of effects on HS biosynthetic enzymes and proteoglycan core proteins, as well as growth factors and their receptors.
2010-12-11 | GSE26010 | GEO
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:Schizophrenia is a complex and severe neuropsychiatric disorder, with a wide range of debilitating symptoms. Several aspects of its multifactorial complexity are still unknown, and some are accepted to be an early developmental deficiency with a more specifically neurodevelopmental origin. Understanding timepoints of disturbances during neural cell differentiation processes could lead to an insight into the development of the disorder. In this context, human brain organoids and neural cells differentiated from patient-derived induced pluripotent stem cells are of great interest as a model to study the developmental origins of the disease. Here we evaluated the differential expression of proteins of schizophrenia patient-derived neural progenitors, early neurons, and brain organoids. Using bottom-up shotgun proteomics with a label-free approach for quantitative analysis. Multiple dysregulated proteins were found in pathways related to synapses, in line with postmortem tissue studies of schizophrenia patients. However, organoids and immature neurons exhibit impairments in pathways never before found in patient-derived induced pluripotent stem cell studies, such as spliceosomes and amino acid metabolism. In conclusion, here we provide comprehensive, large-scale, protein-level data that may uncover underlying mechanisms of the developmental origins of schizophrenia.
2023-03-11 | PXD026593 | Pride