Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

10 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptome analysis of pancreatic progenitors differentiated from H9 human embryonic stem cells and induced pluripotent stem cells derived from a Mitchell-Riley Syndrome patient

ABSTRACT: Skin biopsies were obtained from a patient with Mitchell-Riley syndrome caused by a homozygous frame-shift mutation (c.1129C>T) in the RFX6 gene that leads to a premature stop codon (p.Arg377X). The patient suffered severe pancreatic agenesis, in common with other Mitchell-Riley syndrome patients. Fibroblasts from the biopsy were reprogrammed to generate a human induced pluripotent stem cell (hiPSC) line (MRS2-6). To assess the effects of the mutant RFX6 allele on pancreas formation and identify direct targets of the transcription factor RFX6, MRS2-6 and H9 control human embryonic stem cells (hESC) were differentiated into pancreatic progenitors. Samples were harvested for RNA isolation and whole transcriptome analysis at days 4 (definitive endoderm), 7 and 8 (gut tube), and 12 (pancreatic progenitors).

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Homo sapiens

SUBMITTER: Engin Cukuroglu

PROVIDER: E-MTAB-6626 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Transcriptome analysis of pancreatic endoderm differentiated from induced pluripotent stem cells derived from a patient with Mitchell-Riley Syndrome and her unaffected father

Project description:Skin biopsies were obtained from a patient with Mitchell-Riley syndrome and her unaffected father. The patient suffered neonatal diabetes, anaemia, intrauterine growth restriction, pancreatic hypoplasia and duodenal atresia, in common with other Mitchell-Riley syndrome patients. The disease was found to be caused by a homozygous frame-shift mutation (c.1129C>T) in the RFX6 gene that leads to a premature stop codon (p.Arg377Ter), of which her father is a carrier. Fibroblasts from the biopsies were reprogrammed to generate human induced pluripotent stem cell (hiPSC) lines: two from the patient (MRS2-6 & MRS2-10) and two from the father (F14 & F18). To assess the effects of the mutant RFX6 allele on pancreas formation, these iPSC were differentiated into PDX1+ pancreatic endoderm and samples harvested for RNA isolation and whole transcriptome analysis. The number of biological replicates (independent differentiation experiments) carried out for each cell line are as follows: F14 (2), F18 (2), MRS2-6 (1), MRS2-10 (2). Two technical replicates were sequenced for each independent experiment.

2020-10-23 | E-MTAB-9243 | biostudies-arrayexpress

Expression data from Xenopus anterior gut RFX6 knockdown

Project description:Recently a new neonatal diabetes syndrome, Mitchell-Riley syndrome, was discovered. To identify the genetic cause of the syndrome homozygosity mapping was used, several chromosomal regions were linked to Mitchell-Riley syndrome. In situ hybridization of genes from one such region using model organism Xenopus laevis identified RFX6 as a potential candidate gene; mutant forms of RFX6 were subsequently found in Mitchell-Riley patients. Analysis of the expression pattern of RFX6 in Xenopus development shows it is expressed broadly in the endoderm early in development, and later RFX6 becomes restricted to the endocrine cells of the gut and pancreas. Morpholino knockdown of RFX6 in Xenopus caused a loss of pancreas marker gene expression. Injection of exogenous wild type RFX6 rescued the morpholino phenotype in Xenopus tadpoles. Attempts to rescue the loss-of-function phenotype using mutant forms of RFX6 found in Mitchell-Riley patients were unsuccessful suggesting the changes lead to loss-of-function and could be the cause of Mitchell-Riley syndrome. Microarray analysis of gene expression in knockdown tissue suggested a downregulation in marker genes for lung, stomach and heart, ambiguous results for the liver, and an upregulation in kidney marker gene expression. RT-PCR and in situ hybridization confirms a loss of lung, stomach and heart gene expression, no change in liver marker hex and an upregulation in kidney marker KcnJ1. The fact that the morpholino phenotype affects multiple organs suggests that RFX6 has a broad role early in endoderm development.

2011-01-24 | GSE23642 | GEO

Genome-wide chromatin binding analysis (ChIP-seq) of HA epitope tagged RFX6 protein in human embryonic stem cell derived pancreatic progenitors

Project description:To identify direct transcriptional targets of RFX6, we performed chromatin immunoprecipitation of HA epitope tagged RFX6 followed by massively parallel DNA sequencing (ChIP-seq). Using CRISPR/Cas9 gene editing, the HA epitope was inserted into the 3' end of the RFX6 gene in H9 hESC. Pluripotent cells were then differentiated into PDX1+RFX6+ pancreatic progenitors and endogenous RFX6-HA was immunoprecipitated with an anti-HA antibody. To eliminate background signal caused by non-specific antibody binding, a control experiment using wild-type H9 hESC was performed in parallel.

2020-10-23 | E-MTAB-9335 | biostudies-arrayexpress

Expression data from Xenopus anterior gut RFX6 knockdown

2011-01-24 | E-GEOD-23642 | biostudies-arrayexpress

Regulatory genomics of human embryonic pancreatic progenitors

Project description:Active regulatory regions in the human embryonic pancreatic progenitors were profiled by integration of transcription factor and histone modification ChIP-seq datasets. These were obtained from pancreatic progenitor cells derived in vitro from human embryonic stem cells. The purpose of this work was to study the epigenomic mechanisms involved in pancreas development.

2013-11-15 | E-MTAB-1990 | biostudies-arrayexpress

Transcriptome analysis of self-renewing human pancreatic progenitors derived from pluripotent stem cells

Project description:Human pluripotent stem cells were differentiated into PDX1+/NKX6-1+ Pancreatic Progenitors (PPd15 cells), which were subsequently captured and expanded in culture. These culture Pancreatic Progenitors (cPP cells) were capable of self-renewal and could be passaged up to 20 times. Furthermore, cPP cells were capable of differentiation into multiple pancreatic lineages, including c-peptide+ beta-like cells, both in vitro and in vivo.

2017-06-06 | E-MTAB-5731 | biostudies-arrayexpress

Transcription profiling of mouse wild type R1 and cells expressing Pax4 following induction of pacreatic differentitation

Project description:This experiment is part of the FunGenES project (FunGenES - "Functional Genomics in Embryonic Stem Cells" partially funded by the 6th Framework Programme of the European Union, http://www.fungenes.org). The experiment was conducted at the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK, Gatersleben, Germany) The goal of the experiment is to optimize existing differentiation protocols for endoderm differentiation of ES cells to efficiently generate optimal levels of pancreatic cell types. To characterize potential pancreatic progenitors during the process of induced pancreatic differentiation, wild type R1 cells and R1 cells stably expressing the pancreatic control gene Pax4, RNA samples of undifferentiated cells, pancreatic precursor and differentiated cells were prepared.

2009-03-01 | E-TABM-493 | biostudies-arrayexpress

TEAD and YAP regulate the enhancer network of human embryonic pancreatic progenitors

Project description:The genomic regulatory programs that underlie human organogenesis are poorly understood. Human pancreas development, in particular, has pivotal implications for pancreatic regeneration, cancer, and diabetes. We have now created maps of transcripts, active enhancers, and transcription factor networks in pancreatic multipotent progenitors obtained from human embryos, or derived in vitro from human embryonic stem cells. This revealed that artificial progenitors recapitulate salient transcriptional and epigenomic features of their natural counterparts. Using this resource, we show that TEAD1, a transcription factor controlled by Hippo signaling, is a core component of the combinatorial code of pancreatic progenitor enhancers. TEAD thus activates genes encoding regulators of signaling pathways and stage-specific transcription factors that are essential for normal pancreas development. Accordingly, chemical and genetic perturbations of TEAD and its coactivator YAP inhibited expression of known regulators such as FGFR2 and SOX9, and suppressed the proliferation and expansion of mouse and zebrafish pancreatic progenitors. These findings provide a resource of active enhancers and transcripts in human pancreatic multipotent progenitors, and uncover a central role of TEAD and YAP as signal-responsive regulators of the transcriptional program of early pancreas development.

2015-04-06 | E-MTAB-3061 | biostudies-arrayexpress

Transcriptome analysis of pancreatic progenitors differentiated from H9 human embryonic stem cells and induced pluripotent stem cells derived from a Mitchell-Riley Syndrome patient

Project description:Transcriptome analysis of pancreatic progenitors differentiated from H9 human embryonic stem cells and induced pluripotent stem cells derived from a Mitchell-Riley Syndrome patient

| PRJEB25729 | ENA

RFX6 haploinsufficiency impairs β-cell functionality predisposing to diabetes

Project description:We performed bulk RNA-seq analysis for CRISPR-Cpf1 mutated H1 cells that were differentiated into pancreatic cells. Homozygous mutant was compared to control cells (RFX6-/- vs RFX6+/+) at stage 3 (PF) and stage 5 (EP), and heterozygous mutant was compared to control cells (RFX6-/+ vs RFX6+/+) at stage 7 (SC-islets).

2024-04-11 | GSE234289 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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