Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA375750 | ENA |
REPOSITORIES: ENA
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Project description:Non-coding regions compose most of the human genome, yet their functionality is poorly defined. In the developing human neocortex, non-coding regulatory elements tightly regulate expression to direct neural progenitor proliferation and neurogenesis. Here, we define thousands of non-coding elements involved in human neurogenesis by contrasting chromatin accessibility via ATAC-seq from the germinal zone and cortical plate.
2018-01-11 | GSE95023 | GEO
Project description:<p>Defining the number, proportion, or lineage of distinct cell types in the developing human brain is an important goal of modern brain research. We produced single cell transcriptomic profiles for 40,000 cells at mid-gestation to define deep expression profiles corresponding to all known major cell types at this developmental period and compare this with bulk tissue profiles. We identified multiple transcription factors (TFs) and co-factors expressed in specific cell types, including multiple new cell-type-specific relationships, providing an unprecedented resource for understanding human neocortical development and evolution. This includes the first single-cell characterization of human subplate neurons and subtypes of developing glutamatergic and GABAergic neurons. We also used these data to deconvolute single cell regulatory networks that connect regulatory elements and transcriptional drivers to single cell gene expression programs in the developing CNS. We characterized major developmental trajectories that tie cell cycle progression with early cell fate decisions during early neurogenesis. Remarkably, we found that differentiation occurs on a transcriptomic continuum, so that differentiating cells not only express the few key TFs that drive cell fates, but express broad, mixed cell-type transcriptomes prior to telophase. Finally, we mapped neuropsychiatric disease genes to specific cell types, implicating dysregulation of specific cell types in ASD, ID, and epilepsy, as the mechanistic underpinnings of several neurodevelopmental disorders. Together these results provide an extensive catalog of cell types in human neocortex and extend our understanding of early cortical development, human brain evolution and the cellular basis of neuropsychiatric disease.</p>
| phs001836 | dbGaP
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Changes in gene regulation have been linked to the expansion of the human cerebral cortex and to neurodevelopmental disorders. However, the biological effects of genetic variation within developmental regulatory elements on human corticogenesis are not well understood. We used sgRNA-Cas9 genetic screens in human neural stem cells (hNSCs) to disrupt 10,674 expressed genes and 2,227 enhancers active in the developing human cortex and determine the resulting effects on cellular proliferation. Gene disruptions affecting proliferation were enriched for genes associated with risk for human neurodevelopmental phenotypes including primary microcephaly and autism spectrum disorder. Although disruptions in enhancers had overall weaker effects on proliferation than gene disruptions, we identified enhancer disruptions that severely perturbed hNSC self-renewal. Disruptions in Human Accelerated Regions and Human Gain Enhancers, regulatory elements implicated in the evolution of the human brain, also perturbed hNSC proliferation, establishing a role for these elements in human neurodevelopment. Integrating proliferation phenotypes with chromatin interaction maps revealed regulatory relationships between enhancers and target genes that contribute to neurogenesis and potentially to human cortical evolution.
2019-12-03 | GSE138823 | GEO
Project description:Knockdown of the schizophrenia susceptibility gene TCF4 alters gene expression and proliferation of progenitor cells from the developing human neocortex.
| PRJNA263171 | ENA
Project description:The transcription factor Pax6 acts as a key developmental regulator in various organs. In the developing brain Pax6 regulates patterning, neurogenesis and proliferation, but how these diverse effects are mediated at the molecular level is not well understood. As Pax6 regulates forebrain development including neurogenesis, proliferation and patterning, almost exclusively by one of its DNA-binding domains, the bipartite paired domain, we examined the role of its respective DNA-binding subdomains (PAI and RED). Using mice with point mutations in the PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C) subdomains we unravelled opposing roles of mutations in these subdomains in regulating genes that control proliferation in the developing cerebral cortex. Mutation of the PAI domain reduced proliferation of both apical and basal progenitors, while the RED domain mutation significantly increased proliferation. Conversely, neurogenesis was affected only by the PAI domain mutation phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression analysis supported the molecularly distinct signature upon mutation of these subdomains unravelling the key neurogenic signature mediated by the PAI domain. The altered expression of genes identified as direct Pax6 targets by chromatin immunoprecipitation allowed to further identify regulatory elements whose function was impaired by each individual Pax6 mutated protein. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing distinct subdomains to regulate neurogenesis and exert opposing effects on proliferation, while Pax6-target genes involved in patterning tolerate either subdomain mutation. We performed gene expression microarray analysis of Pax6 mutant mice (Leca2, Leca4, Sey) and control mice
2013-03-19 | E-GEOD-35260 | biostudies-arrayexpress
Project description:<p>Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. To obtain a high resolution depiction of chromatin structure and gene expression in developing human fetal cortex, we dissected the post-conception week (PCW) 15-17 human neocortex into two major anatomical divisions to distinguish between proliferating neural progenitors and post mitotic neurons: (1) GZ: the neural progenitor-enriched region encompassing the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ) and (2) CP: the neuron-enriched region containing the subplate (SP), cortical plate (CP), and marginal zone (MZ). Tissues were obtained from three independent donors and three to four technical replicates from each tissue were processed for ATAC-seq to define the landscape of accessible chromatin and RNA-seq for genome-wide gene expression profiling.</p>
| phs001438 | dbGaP
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:SRSF10 regulates proliferation of neural progenitor cells and affects neurogenesis in the developing mouse neocortex
| PRJNA936877 | ENA