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Dataset Information

Gene expression from Gaucher Disease iPSc

ABSTRACT: Gene expression data obtained from induced pluripotent stem cells derived from wild type fibroblasts (iPSc WT) and from Gaucher Disease type 2 fibroblasts (GD iPSc). Also, gene expression analysis from the initial fibroblasts was made (WT fibroblasts and GD- fibroblasts), as well as gene expression analysis from a human embryonic stem cell line (hES4). Two different iPSc cell lines derived from Gaucher Disease type 2 fibroblasts were analysed in order to be compared to iPSc derived from Wild Type fibroblasts (only one cell line) and human embryonic stem cells (only one cell line). The initial cells: two different wild type fibroblasts and one Gaucher disease type 2 fibroblasts were also analysed.

ORGANISM(S): Homo sapiens

SUBMITTER: Erika Lorenzo Vivas

PROVIDER: E-GEOD-41243 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Neuronopathic Gaucher's disease: induced pluripotent stem cells for disease modelling and testing chaperone activity of small compounds.

Tiscornia Gustavo G Vivas Erika Lorenzo EL Matalonga Leslie L Berniakovich Ina I Barragán Monasterio Montserrat M Eguizábal Cristina C Gort Laura L González Federico F Ortiz Mellet Carmen C García Fernández José Manuel JM Ribes Antonia A Veiga Anna A Izpisua Belmonte Juan Carlos JC

Human molecular genetics 20121031 4

Gaucher's disease (GD) is caused by mutations in the GBA1 gene, which encodes acid-β-glucosidase, an enzyme involved in the degradation of complex sphingolipids. While the non-neuronopathic aspects of the disease can be treated with enzyme replacement therapy (ERT), the early-onset neuronopathic form currently lacks therapeutic options and is lethal. We have developed an induced pluripotent stem cell (iPSc) model of neuronopathic GD. Dermal fibroblasts of a patient with a P.[LEU444PRO];[GLY202AR ...[more]

PMID: 23118351

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Project description:In non-neuronopathic type 1 Gaucher disease (GD1) mutations in GBA1 gene results in deficiency of glucocerebrosidase and the accumulation of glucocerebroside in lysosomes of mononuclear phagocytes. The metabolic defect leads to a complex phenotype involving the viscera, the bone marrow and the skeleton. However the prevailing macrophage-centric view of the disease does not explain emerging aspects of the disease such as hematological malignancies, autoimmune diathesis, ParkinsonM-bM-^@M-^Ys disease and osteoporosis poorly responsive to macrophage targeted enzyme therapy or anti-resorptive therapies. We developed a conditional KO mouse model of GD1 to delineate cells and pathways in GD1. By targeting the cells of the hematopoetic and mesenchymal cell lineages through an Mx1 promoter, we recapitulated human GD1. We show that, in addition to significant visceral and hematologic disease, GD1 mice show profound osteopenia due to a bone formation defect. Cytokine measurements, microarray analysis and cellular immunophenotyping together point to widespread dysfunction of macrophages and other immune cells together with a striking abnormality in thymic T-cell development. Our study provides the first direct evidence for the involvement of cell lineages other than mononuclear phagocytes, most notably osteoblasts and T cells, in the pathophysiology of the clinical spectrum of type 1 GD. These findings have important implications for treatment of GD1. We hypothesize that regulation of gene expression is different in Gaucher disease compared with the normal controls. This difference may even be evident in the different stages of this disease. In order to gain insight to the genes that are potentially involved in the development of Gaucher disease in its different clinical stages, exon-array is chosen for this genome-wide association studies. Mouse liver and spleen samples from normal control, GD with moderate to severe splenomegaly/hepatomegaly, together nine samples were chosen. The goal is to find out genes of which the expression may relate to the GD or the severity of GD and thus help identify genetic modifier genes that may contribute to the onset and development of Gaucher disease.

Dataset Information

Gene expression from Gaucher Disease iPSc

Publications

Neuronopathic Gaucher's disease: induced pluripotent stem cells for disease modelling and testing chaperone activity of small compounds.

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