Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA396881 | ENA |
REPOSITORIES: ENA
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Project description:Recent studies on developing three-dimensional (3D) brain organoids from stem cells have allowed the generation of in vitro models of neural disease and have enabled the screening of drugs because these organoids mimic the complexity of neural tissue. Niemann-Pick disease, type C (NPC) is a neurodegenerative lysosomal storage disorder caused by mutations in the NPC1 protein. The pathological features underlying NPC are characterized by the abnormal accumulation of cholesterol in acidic compartments, including late endosomes and lysosomes. Due to the inaccessibility of brain tissues from human NPC patients, we developed NPC brain organoids with induced neural stem cells from NPC patient-derived fibroblasts. NPC organoids exhibit significantly reduced size and proliferative ability, which are accompanied by accumulation of cholesterol, impairment in neuronal differentiation and autophagic flux and dysfunction of lysosomes; therefore, NPC organoids can recapitulate the main phenotypes of NPC patients. Furthermore, these pathological phenotypes observed in NPC organoids were reversed by treatment with valproic acid, which is known to be an effective treatment for several neurodegenerative diseases. Our data present patient-specific phenotypes in 3D organoid-based models of NPC and highlight the application of this model to drug screening in vitro.
2020-12-21 | GSE157676 | GEO
Project description:Brain microenvironment plays an important role in neurodevelopment and function, where extracellular matrix (ECM) components and soluble factors modulate cellular features, as migration, proliferation survival and neuronal function. Disruption of microenvironment’s homeostasis is often related to pathological conditions. Here, we addressed the microenvironment remodeling occurring during in vitro differentiation of human neural stem cells (NSC) in a three-dimensional (3D) culture system. Proteome and transcriptome dynamics revealed significant changes namely at cell membrane and ECM composition during 3D differentiation, diverging significantly from the profile of monolayer cultures (2D). Structural proteoglycans typically found in brain ECM were enriched during 3D differentiation, while 2D cultures presented increased levels of basement membrane constituents (e.g., laminins, collagens and fibrillins). Moreover, higher expression levels of synaptic machinery and ion transport machinery constituents observed for 3D cultures, both at mRNA and protein levels, suggested a higher degree of neuronal maturation and organization relative to 2D differentiation. This work demonstrated that neural cellular and extracellular features can be recapitulated in the presented 3D neural cell model, highlighting its value to address molecular defects in cell-ECM interactions associated with neurological disorders. <html><head>Associated GEO dataset is available at</head><body><a href="https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi">GSE102139</a></body></html>
2018-07-31 | PXD007130 | Pride
Project description:To understand regulatory function in human neural differentiation, we performed ATAC-seq in human induced pluripotent stem cells (iPSC), in vitro-differentiated neural progenitor cells (NPC) and ganglionic eminence-like (GE) cells, as well as commercially available neural stem cells, GABAergic neurons, and glutamatergic neurons. We also performed circular chromosome conformation capture (4C)-seq on these cells.
2021-05-20 | GSE174727 | GEO
Project description:Many studies have compared the genetic and epigenetic profiles of human induced pluripotent stem cells (hiPSCs) to human embryonic stem cells (hESCs) and yet the picture remains unclear. To address this, we derived a population of neural precursor cells (NPCs) from the H1 (WA01) hESC line and generated isogenic iPSC lines by reprogramming. The gene expression and methylation profile of three lines were compared to the parental line and intermediate NPC population. We found no gene probe with expression that differed significantly between hESC and iPSC samples under undifferentiated or differentiated conditions. Analysis of the global methylation pattern also showed no significant difference between the two PSC populations. Both undifferentiated populations were distinctly different from the intermediate NPC population in both gene expression and methylation profiles. One point to note is that H1 is a male line and so extrapolation to female lines should be cautioned. However, these data confirm our previous findings that there are no significant differences between hESCs and hiPSCs at the gene expression or methylation level. 22 samples: 1 human NPC, 2 human ESC (UNDIFF), 5 human iPSC (UNDIFF), 2 human ESC (EB_ecto), 5 human iPSC (EB_ecto), 2 human ESC (EB_mesend), 5 human iPSC (EB_mesend)
2014-01-01 | E-GEOD-51561 | biostudies-arrayexpress
Project description:Induced pluripotent stem cell-derived neural progenitor cells (iPSC-NPCs) are a promising source of tailor-made cell therapy for neurological diseases. However, tumorigenicity and immunogenicity are major obstacles to translational use. Here we demonstrate epidural therapeutics of human iPSC-NPC grafts after experimental ischemic stroke to avoid surgical damage and intracerebral teratomas. We found that human iPSC-NPCs co-cultured trans-membranously with rat cortical cells subjected to oxygen-glucose deprivation, compared with human mesenchymal stem cells from bone marrow and umbilical cord Wharton's jelly, superiorly enhanced neural survival and growth as well as mitigated astrogliosis. Using comparative whole-genome microarrays and cytokine arrays, we identified a neurorestorative secretome from iPSC-NPCs and neutralization of the enriched cytokines potently abolished the neuroprotective effects in the iPSC-NPC co-cultures. Moreover, we implanted the human iPSC-NPCs epidurally using fibrin glue over the peri-infarct cortex at 7 days following permanent middle cerebral artery occlusion in adult rats. The cell-treated rats showed significant improvement in their paretic forelimb usage and grip strength from 10 days post-transplantation (dpt) onwards compared to the vehicle-treated rats, accompanied by ameliorated infarct/atrophy volumes, inflammatory infiltration and astrogliosis, as well as augmented angiogenesis, oligodendrocyte precursor cells and white matter integrity. Some iPSC-NPCs migrated into the peri-infarct cortex but poorly survived by 21 dpt. This proof-of-concept study demonstrates that a less invasive yet effective epidural delivery route of human iPSC-NPCs may promote functional remodeling of the peri-infarct brain predominantly through distinct paracrine effects. cDNA samples from iPSC-NPC were hybridized to the human genome U133 Plus 2.0 GeneChip arrays.
2016-06-02 | E-GEOD-82101 | biostudies-arrayexpress
Project description:Many studies have compared the genetic and epigenetic profiles of human induced pluripotent stem cells (hiPSCs) to human embryonic stem cells (hESCs) and yet the picture remains unclear. To address this, we derived a population of neural precursor cells (NPCs) from the H1 (WA01) hESC line and generated isogenic iPSC lines by reprogramming. The gene expression and methylation profile of three lines were compared to the parental line and intermediate NPC population. We found no gene probe with expression that differed significantly between hESC and iPSC samples under undifferentiated or differentiated conditions. Analysis of the global methylation pattern also showed no significant difference between the two PSC populations. Both undifferentiated populations were distinctly different from the intermediate NPC population in both gene expression and methylation profiles. One point to note is that H1 is a male line and so extrapolation to female lines should be cautioned. However, these data confirm our previous findings that there are no significant differences between hESCs and hiPSCs at the gene expression or methylation level. 12 samples: 1 human NPC, 5 human ESC (UNDIFF), 6 human iPSC (UNDIFF)
2014-01-01 | E-GEOD-51747 | biostudies-arrayexpress
Project description:Lineage specific transcription factors (TF) define and reinforce tissue specific cell types. For instance, stable endoderm progenitors were established from human ESC by constitutive expression of SOX7 or SOX17. We hypothesized that combinatorial expression of OCT4, SOX2 and KLF4M-BM- together with the neural-lineage TF, Zic3, could directly convert fibroblasts into stable neuronal progenitor cells (NPC). Ensuing colonies predominantly expressed genes present in human NPC, as demonstrated by genome wide transcriptional analysis, and this phenotype could be maintained through many passages.M-BM- When injected in immunodeficient mice, Zic3-induced (Zi)NPC form neuroendocrine tumors without evidence of mesoderm or endoderm. In vitro, ZiNPC spontaneously differentiated to neural cells only, and could be differentiated into astrocytes, oligodendrocytes and motor neuron lineages. In conclusion, addition of Zic3 during induced pluripotent stem cell (iPSC) generation, allows for the derivation of stable neural lineage progenitor cells. 3 hESC, 3 hESC-derived neurosphere and 3 ZiNPC samples were analyzed
2012-05-21 | E-GEOD-29770 | biostudies-arrayexpress
Project description:CRISPR-edited human induced pluripotent stem cell (iPSC)-derived glioma models provide a robust platform to investigate the biology of these aggressive tumors in an isogenic background or to test possible treatments in preclinical settings. We created iPSC12 lines that carry different combinations of glioma driver mutations using CRISPR/Cas9 genome editing technology, including TP53-/-, ATRX-/-, IDH1-R132H/WT, PTEN-/-, CDKN2A/B-/-, TERT promoter(TERTp) C228T/WT, MTAP-/-, and overexpression (OE) of EGFRvIII oncogenic isoform. Edited iPSCs were then differentiated into neural progenitor cells (NPC) using a small molecule protocol. We cultured the edited NPCs in 3D organoid with an FBS-containing differentiation medium. After 14 days, different genotypes of NPCs formed organoids were harvest and RNAs were isolated and subjected to RNA-seq analysis. To create an in vivo model system, NPCs with different genotypes were intracranially transplanted into athymic mice. Mice were sacrificed when pathologic symptoms developed resulting from tumor burden or 120 days post brain transplantation. RNAs were extracted from the tumor region of brain tissue sections and subjected to RNA-seq analysis. Our study showed that the iPSC-based model of gliomas displayed distinct mutation-dependent variation in transcriptome, which recapitulated the gene expression signatures of human gliomas.
2024-05-15 | GSE212671 | GEO
Project description:Activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox-2, Oct3/4, C-MyC and Klf-4. The derived NSC could be differentiated to astroglia and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. 11 Human samples from 7 sources representing 4 different cell types: 2 CD34 (CD34+ cells purified from adult peripheral blood), 3 iNS (induced Neural Stem Cells derived directly from CD34+ cells), 2 iNS derived from iPSC (Neural Stem cells differentiated from induced Pluripotent Stem Cells from CD34+ cells), 4 NPC (human primary cultured neural progenitor cells)
2014-01-01 | E-GEOD-44532 | biostudies-arrayexpress
Project description:ATAC-seq samples from 2 species and 2 cell types were generated to study cis-regulatory element evolution. Briefly, previously generated urinary stem cell derived iPS-cells (Homo sapiens) of 2 human individuals and fibroblast derived cynomolgus macaque iPSCs (Macaca fascicularis) of 2 individuals (Geuder et al. 2021) were differentiated to neural progenitor cells via dual-SMAD inhibition as three-dimensional aggregation culture (Chambers et al. 2009; Ohnuki et al. 2014). The NPC lines were cultured in NPC proliferation medium and passaged 2 - 4 times until they were dissociated and subjected to ATAC-seq together with the respective iPSC clones. ATAC-seq libraries were generated using the Omni-ATAC protocol (Corces et al. 2017) with minor modifications.
2023-10-25 | E-MTAB-13373 | biostudies-arrayexpress