Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE74885 | GEO | 2016/11/10

SECONDARY ACCESSION(S): PRJNA301723

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia.

Project description:Patients with an HNF1B(S148L/+) mutation (MODY5) typically exhibit pancreatic hypoplasia. However, the molecular mechanisms are unknown due to inaccessibility of patient material and because mouse models do not fully recapitulate MODY5. Here, we differentiated MODY5 human-induced pluripotent stem cells (hiPSCs) into pancreatic progenitors, and show that the HNF1B(S148L/+) mutation causes a compensatory increase in several pancreatic transcription factors, and surprisingly, a decrease in PAX6 pancreatic gene expression. The lack of suppression of PDX1, PTF1A, GATA4, and GATA6 indicates that MODY5-mediated pancreatic hypoplasia is mechanistically independent. Overexpression studies demonstrate that a compensatory increase in PDX1 gene expression is due to mutant HNF1B(S148L/+) but not wild-type HNF1B or HNF1A. Furthermore, HNF1B does not appear to directly regulate PAX6 gene expression necessary for glucose tolerance. Our results demonstrate compensatory mechanisms in the pancreatic transcription factor network due to mutant HNF1B(S148L/+) protein. Thus, patients typically develop MODY5 but not neonatal diabetes despite exhibiting pancreatic hypoplasia.

| S-EPMC4788763 | biostudies-literature

Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia

Project description:Early Developmental Perturbations in a Human Stem Cell Model of MODY5/HNF1B Pancreatic Hypoplasia

| PRJNA301723 | ENA

Modeling HNF1B-associated monogenic diabetes using human iPSCs reveals an early stage impairment of the pancreatic developmental program.

Project description:Heterozygous mutations in HNF1B in humans result in a multisystem disorder, including pancreatic hypoplasia and diabetes mellitus. Here we used a well-controlled human induced pluripotent stem cell pancreatic differentiation model to elucidate the molecular mechanisms underlying HNF1B-associated diabetes. Our results show that lack of HNF1B blocks specification of pancreatic fate from the foregut progenitor (FP) stage, but HNF1B haploinsufficiency allows differentiation of multipotent pancreatic progenitor cells (MPCs) and insulin-secreting β-like cells. We show that HNF1B haploinsufficiency impairs cell proliferation in FPs and MPCs. This could be attributed to impaired induction of key pancreatic developmental genes, including SOX11, ROBO2, and additional TEAD1 target genes whose function is associated with MPC self-renewal. In this work we uncover an exhaustive list of potential HNF1B gene targets during human pancreas organogenesis whose downregulation might underlie HNF1B-associated diabetes onset in humans, thus providing an important resource to understand the pathogenesis of this disease.

| S-EPMC8452540 | biostudies-literature

A developmental model of human early cardiac valvulogenesis

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-01-23 | GSE73620 | GEO

Loss of FGF9 in mice leads to pancreatic hypoplasia and asplenia

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-03-28 | GSE210646 | GEO

An epigenetic signature of developmental potential in neural stem cells and early neurons

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

2013-06-09 | E-GEOD-46793 | biostudies-arrayexpress

Human induced pluripotent stem cells reveal early developmental molecular correlates with a probable Leber congenital amaurosis type I

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

2015-01-21 | E-GEOD-43946 | biostudies-arrayexpress

Charting Brachyury-mediated Developmental Pathways During Early Mouse Embryogenesis

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

2014-03-10 | E-GEOD-54985 | biostudies-arrayexpress

An epigenetic signature of developmental potential in neural stem cells and early neurons

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-06-09 | GSE46793 | GEO

Arabidopsis transcriptome responses to mitochondrial perturbations

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

2013-01-01 | E-GEOD-29269 | biostudies-arrayexpress

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