Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE66078 | GEO | 2015/04/15

SECONDARY ACCESSION(S): PRJNA275833

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2015-04-15 | E-GEOD-66078 | biostudies-arrayexpress

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells [HumanMethylation450]

2015-04-15 | GSE66077 | GEO

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells [HumanMethylation450]

Project description:We monitored 9 pluripotent stem cell lines across three time points of hepatic directed differentiation, representing 3 developmental stages: undifferentiated (T0), definitive endoderm (T5), and early hepatocyte (T24). ESCs (n=3) and patient-derived normal (n=3) or PiZZ (n=3) iPSCs were analyzed in the undifferentiated state (T0), after differentiation to definitive endoderm (T5), and upon reaching hepatic stage (T24) for a total of 27 samples. We sought to test the hypothesis that a single transgene-free iPSC clone from each donor could be used to detect disease-specific differences between the normal cohort and the PiZZ cohort, anticipating that this difference would emerge only at a developmental stage in which the mutant AAT gene is expressed. Cells were sorted before analysis at T0 and T5 after antibody staining for TRA1-80+/SSEA3+ (T0) or C-kit+/CXCR4+ (T5) cells. ESCs (n=3) and patient-derived normal (n=3) or PiZZ (n=3) iPSCs were analyzed in the undifferentiated state (T0), after differentiation to definitive endoderm (T5), and upon reaching hepatic stage (T24) for a total of 27 samples. Cells were sorted before analysis at T0 and T5 after antibody staining for TRA1-80+/SSEA3+ (T0) or C-kit+/CXCR4+ (T5) cells. RNA was extracted at each stage, biotin labeled, and hybridized to either Affymetrix GeneChip Human Gene 1.0 ST or miRNA 2.0 arrays. For methylation analysis, gDNA was sorted from the same 27 samples before undergoing bisulfite conversion. Bisulfite converted DNA was then amplified and purified prior to overnight hybridization to Illumina’s Infinium HumanMethylation 450 BeadChips. Next day staining of hybridized arrays produced methylation-dependent differential fluorescence that was detected via an Illumina iScan array scanner.

2015-04-15 | E-GEOD-66077 | biostudies-arrayexpress

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells [miRNA-2_0]

2015-04-15 | GSE66075 | GEO

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells [miRNA-2_0]

2015-04-15 | E-GEOD-66075 | biostudies-arrayexpress

Emergence of a stage-dependent human liver disease signature with directed differentiation of alpha-1 antitrypsin-deficient iPS cells.

Project description:Induced pluripotent stem cells (iPSCs) provide an inexhaustible source of cells for modeling disease and testing drugs. Here we develop a bioinformatic approach to detect differences between the genomic programs of iPSCs derived from diseased versus normal human cohorts as they emerge during in vitro directed differentiation. Using iPSCs generated from a cohort carrying mutations (PiZZ) in the gene responsible for alpha-1 antitrypsin (AAT) deficiency, we find that the global transcriptomes of PiZZ iPSCs diverge from normal controls upon differentiation to hepatic cells. Expression of 135 genes distinguishes PiZZ iPSC-hepatic cells, providing potential clues to liver disease pathogenesis. The disease-specific cells display intracellular accumulation of mutant AAT protein, resulting in increased autophagic flux. Furthermore, we detect beneficial responses to the drug carbamazepine, which further augments autophagic flux, but adverse responses to known hepatotoxic drugs. Our findings support the utility of iPSCs as tools for drug development or prediction of toxicity.

| S-EPMC4437473 | biostudies-literature

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells [HuGene-1_0-st]

2015-04-15 | GSE66076 | GEO

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells [HuGene-1_0-st]

2015-04-15 | E-GEOD-66076 | biostudies-arrayexpress

Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells

Project description:Emergence of a developmental stage-dependent human liver disease signature demonstrated by directed differentiation of alpha-1 antitrypsin deficient iPS cells

| PRJNA275833 | ENA

Alpha-1 Antitrypsin Substitution for Extrapulmonary Conditions in Alpha-1 Antitrypsin Deficient Patients.

Project description:Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder which most commonly manifests as pulmonary emphysema. Accordingly, alpha-1 antitrypsin (AAT) augmentation therapy aims to reduce the progression of emphysema, as achieved by life-long weekly slow-drip infusions of plasma-derived affinity-purified human AAT. However, not all AATD patients will receive this therapy, due to either lack of medical coverage or low patient compliance. To circumvent these limitations, attempts are being made to develop lung-directed therapies, including inhaled AAT and locally-delivered AAT gene therapy. Lung transplantation is also an ultimate therapy option. Although less common, AATD patients also present with disease manifestations that extend beyond the lung, including vasculitis, diabetes and panniculitis, and appear to experience longer and more frequent hospitalization times and more frequent pneumonia bouts. In the past decade, new mechanism-based clinical indications for AAT therapy have surfaced, depicting a safe, anti-inflammatory, immunomodulatory and tissue-protective agent. Introduced to non-AATD individuals, AAT appears to provide relief from steroid-refractory graft-versus-host disease, from bacterial infections in cystic fibrosis and from autoimmune diabetes; preclinical studies show benefit also in multiple sclerosis, ulcerative colitis, rheumatoid arthritis, acute myocardial infarction and stroke, as well as ischemia-reperfusion injury and aberrant wound healing processes. While the current augmentation therapy is targeted towards treatment of emphysema, it is suggested that AATD patients may benefit from AAT augmentation therapy geared towards extrapulmonary pathologies as well. Thus, development of mechanism-based, context-specific AAT augmentation therapy protocols is encouraged. In the current review, we will discuss extrapulmonary manifestations of AATD and the potential of AAT augmentation therapy for these conditions.

| S-EPMC6361480 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data