Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Human stem cell models: lessons for pancreatic development and disease.

ABSTRACT: A comprehensive understanding of mechanisms that underlie the development and function of human cells requires human cell models. For the pancreatic lineage, protocols have been developed to differentiate human pluripotent stem cells (hPSCs) into pancreatic endocrine and exocrine cells through intermediates resembling in vivo development. In recent years, this differentiation system has been employed to decipher mechanisms of pancreatic development, congenital defects of the pancreas, as well as genetic forms of diabetes and exocrine diseases. In this review, we summarize recent insights gained from studies of pancreatic hPSC models. We discuss how genome-scale analyses of the differentiation system have helped elucidate roles of chromatin state, transcription factors, and noncoding RNAs in pancreatic development and how the analysis of cells with disease-relevant mutations has provided insight into the molecular underpinnings of genetically determined diseases of the pancreas.

SUBMITTER: Gaertner B

PROVIDER: S-EPMC6824472 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Human stem cell models: lessons for pancreatic development and disease.

Gaertner Bjoern B Carrano Andrea C AC Sander Maike M

Genes & development 20191101 21-22

A comprehensive understanding of mechanisms that underlie the development and function of human cells requires human cell models. For the pancreatic lineage, protocols have been developed to differentiate human pluripotent stem cells (hPSCs) into pancreatic endocrine and exocrine cells through intermediates resembling in vivo development. In recent years, this differentiation system has been employed to decipher mechanisms of pancreatic development, congenital defects of the pancreas, as well as ...[more]

PMID: 31676735

Similar Datasets

Lessons in human biology from a monogenic pancreatic β cell disease.

Project description:Deciphering the complexities of human β cell physiology is critical to our understanding of the pathophysiology behind both type 1 and type 2 diabetes. One way to do this is to study individuals with congenital hyperinsulinism (CHI), a rare genetic disease characterized by dysregulation of insulin secretion resulting in hypoglycemia. In this issue of the JCI, Henquin et al. report in vitro studies of pancreatic tissue obtained from CHI patients during therapeutic pancreatectomy that have yielded exciting new insights into human β cell physiology. The data validate and extend observations made in model organisms.

| S-EPMC3195485 | biostudies-literature

Pluripotent stem cell disease modeling of GATA6 haploinsufficiency in human pancreatic development

Project description:To better understand molecular mechanisms of human pancreatic development associated with GATA6 haploinsufficiency, we performed RNA-seq analysis to characterize the biological processes affected by GATA6 heterozygous mutation. We found majority of top downregulated transcription factors are known to play key roles in pancreatic development and top downregulated genes were enriched with factors involved in developmental processes, with the pancreas being the top affected lineage.

2017-02-20 | GSE92581 | GEO

Pluripotent stem cell disease modeling of GATA6 haploinsufficiency in human pancreatic development

Project description:To better understand molecular mechanisms of human pancreatic development associated with GATA6 haploinsufficiency, we performed RNA-seq analysis to characterize the biological processes affected by GATA6 heterozygous mutation. We identified 542 differential expression genes in the mutants, of which 310 were downregulated. Gene ontology analysis showed that top downregulated transcription factors were associated with developmental process.

2016-12-15 | GSE76025 | GEO

Challenges in mucosal HIV vaccine development: lessons from non-human primate models.

Project description:An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinical studies in non-human primate models have facilitated progress in mucosal vaccine development by evaluating candidate vaccine approaches, developing methodologies for collecting and assessing mucosal samples, and providing clues to immune correlates of protective immunity for further investigation. In this review we have focused on non-human primate studies which have provided important information for future design of vaccine strategies, targeting of mucosal inductive sites, and assessment of mucosal immunity. Knowledge gained in these studies will inform mucosal vaccine design and evaluation in human clinical trials.

| S-EPMC4147690 | biostudies-literature

Human hematopoietic stem cell maintenance and myeloid cell development in next-generation humanized mouse models.

Project description: Not available

| S-EPMC6373748 | biostudies-literature

Human disease models in drug development.

Project description:Biomedical research is undergoing a paradigm shift towards approaches centred on human disease models owing to the notoriously high failure rates of the current drug development process. Major drivers for this transition are the limitations of animal models, which, despite remaining the gold standard in basic and preclinical research, suffer from interspecies differences and poor prediction of human physiological and pathological conditions. To bridge this translational gap, bioengineered human disease models with high clinical mimicry are being developed. In this Review, we discuss preclinical and clinical studies that benefited from these models, focusing on organoids, bioengineered tissue models and organs-on-chips. Furthermore, we provide a high-level design framework to facilitate clinical translation and accelerate drug development using bioengineered human disease models.

| S-EPMC10173243 | biostudies-literature

A TALEN genome-editing system for generating human stem cell-based disease models.

Project description:Transcription activator-like effector nucleases (TALENs) are a new class of engineered nucleases that are easier to design to cleave at desired sites in a genome than previous types of nucleases. We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types. We demonstrate cell-autonomous phenotypes directly linked to disease-dyslipidemia, insulin resistance, hypoglycemia, lipodystrophy, motor-neuron death, and hepatitis C infection. We found little evidence of TALEN off-target effects, but each clonal line nevertheless harbors a significant number of unique mutations. Given the speed and ease with which we were able to derive and characterize these cell lines, we anticipate TALEN-mediated genome editing of human cells becoming a mainstay for the investigation of human biology and disease.

| S-EPMC3570604 | biostudies-other

Pre-clinical Investigation of Rett Syndrome Using Human Stem Cell-Based Disease Models.

Project description:Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, mostly caused by mutations in MECP2. The disorder mainly affects girls and it is associated with severe cognitive and physical disabilities. Modeling RTT in neural and glial cell cultures and brain organoids derived from patient- or mutation-specific human induced pluripotent stem cells (iPSCs) has advanced our understanding of the pathogenesis of RTT, such as disease-causing mechanisms, disease progression, and cellular and molecular pathology enabling the identification of actionable therapeutic targets. Brain organoid models that recapitulate much of the tissue architecture and the complexity of cell types in the developing brain, offer further unprecedented opportunity for elucidating human neural development, without resorting to conventional animal models and the limited resource of human neural tissues. This review focuses on the new knowledge of RTT that has been gleaned from the iPSC-based models as well as limitations of the models and strategies to refine organoid technology in the quest for clinically relevant disease models for RTT and the broader spectrum of neurodevelopmental disorders.

| S-EPMC8423999 | biostudies-literature

Zebrafish models of human liver development and disease.

Project description:The liver performs a large number of essential synthetic and regulatory functions that are acquired during fetal development and persist throughout life. Their disruption underlies a diverse group of heritable and acquired diseases that affect both pediatric and adult patients. Although experimental analyses used to study liver development and disease are typically performed in cell culture models or rodents, the zebrafish is increasingly used to complement discoveries made in these systems. Forward and reverse genetic analyses over the past two decades have shown that the molecular program for liver development is largely conserved between zebrafish and mammals, and that the zebrafish can be used to model heritable human liver disorders. Recent work has demonstrated that zebrafish can also be used to study the mechanistic basis of acquired liver diseases. Here, we provide a comprehensive summary of how the zebrafish has contributed to our understanding of human liver development and disease.

| S-EPMC4784975 | biostudies-other

Development of murine bariatric surgery models: lessons learned.

Project description:Roux-en-Y gastric bypass (RYGB) improves comorbidities such as diabetes and hypertension and lowers the risk of obesity-related cancers. To better understand the physiologic and genetic influences of bariatric surgery, a reliable murine model is needed that can be extended to genetically engineered mice. Given the complexity of these procedures, few researchers have successfully implemented these techniques beyond larger rodent models. The purpose of our study was to develop a technically feasible and reproducible murine model for RYGB and sleeve gastrectomy (SG). Mice were converted to liquid diet perioperatively without fasting and housed in groups on raised wire platforms. SG involved significant reduction of stomach volume followed by multilayer repair of the gastrotomy. RYGB procedure consisted of side-to-side, functional end-to-side bowel anastomoses and exclusion of the stomach medial to the gastroesophageal junction. Sham surgeries consisted of enterotomies and gastrotomy followed by primary repair without resection or rerouting. Survival after incorporation of the aforementioned techniques was 100% in the SG group and 41% in the RYGB group at 1 mo after surgery. Only 26% of RYGB mortality was attributed to leak, obstruction, or stricture; the majority of postoperative mortality was due to stress, dumping, or malnutrition. Much of the survival challenge for this surgical model was related to perioperative husbandry, which is to be expected given their small stature and poor response to stress. Utilization of the perioperative and surgical techniques described will increase survival and feasibility of these technically challenging procedures, allowing for a better understanding of mechanisms to explain the beneficial effects of bariatric surgery.

| S-EPMC6298430 | 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