Advertisement

Topics

HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells.

08:00 EDT 27th May 2019 | BioPortfolio

Summary of "HNF4A Haploinsufficiency in MODY1 Abrogates Liver and Pancreas Differentiation from Patient-Derived Induced Pluripotent Stem Cells."

Maturity-onset diabetes of the young 1 (MODY1) is a monogenic diabetes condition caused by heterozygous HNF4A mutations. We investigate how HNF4A haploinsufficiency from a MODY1/HNF4A mutation influences the development of foregut-derived liver and pancreatic cells through differentiation of human induced pluripotent stem cells from a MODY1 family down the foregut lineage. In MODY1-derived hepatopancreatic progenitors, which expressed reduced HNF4A levels and mislocalized HNF4A, foregut genes were downregulated, whereas hindgut-specifying HOX genes were upregulated. MODY1-derived hepatocyte-like cells were found to exhibit altered morphology. Hepatic and β cell gene signatures were also perturbed in MODY1-derived hepatocyte-like and β-like cells, respectively. As mutant HNF4A (p.Ile271fs) did not undergo complete nonsense-mediated decay or exert dominant negativity, HNF4A-mediated loss of function is likely due to impaired transcriptional activation of target genes. Our results suggest that in MODY1, liver and pancreas development is perturbed early on, contributing to altered hepatic proteins and β cell defects in patients.

Affiliation

Journal Details

This article was published in the following journal.

Name: iScience
ISSN: 2589-0042
Pages: 192-205

Links

DeepDyve research library

PubMed Articles [7642 Associated PubMed Articles listed on BioPortfolio]

Ferroptosis is governed by differential regulation of transcription in liver cancer.

Ferroptosis is an outcome of metabolic disorders and closely linked to liver cancer. However, the mechanism underlying the fine regulation of ferroptosis in liver cancer remains unclear. Here, we have...

HNF4A is essential for the active epigenetic state at enhancers in mouse liver.

Cell fate determination is influenced by interactions between master transcription factors (TFs) and cis-regulatory elements. Hepatocyte nuclear factor 4 alpha (HNF4A), a liver-enriched TF, acts as a ...

Regulation of the pancreatic exocrine differentiation program and morphogenesis by Onecut 1/Hnf6.

The Onecut 1 transcription factor (Oc1, a.k.a. HNF6) promotes differentiation of endocrine and duct cells of the pancreas; however, it has no known role in acinar cell differentiation. We sought to be...

"Liver and pancreas oriented" strategies for minimally invasive surgery of biliary malignant tumors.

Surgery of biliary malignant tumors is highly related to the liver and pancreas. The "Liver and pancreas oriented" characteristics are unavoidable challenges when formulating surgical strategies. In t...

Exceptional diazoxide sensitivity in hyperinsulinaemic hypoglycaemia due to a novel HNF4A mutation.

Diazoxide is the first-line treatment for patients with hyperinsulinaemic hypoglycaemia (HH). Approximately 50% of patients with HH are diazoxide resistant. However, marked diazoxide sensitivity resul...

Clinical Trials [3965 Associated Clinical Trials listed on BioPortfolio]

Liver, Pancreas and Thyroid Function in Burn Patients

The purpose of this study is to determine the extent to which severe burn injuries affect the morphology and function of liver, pancreas and thyroid. The evaluation of the liver will be pe...

A Prospective, Randomized, Single Blind, Multicentre Phase III Study on Organ Preservation With Custodiol-N Solution Compared With Custodiol Solution in Or-gan Transplantation (Kidney, Liver and Pancreas)

Synopsis Title of Study A prospective, randomized, single blind multicentre phase III study on organ preser-vation with Custodiol-N compared with Custodiol solution in organ transplantatio...

Acute Normovolemic Hemodilution Versus Standard Intraoperative Management in Patients Having Hepatic Resection and Pancreaticoduodenectomy

With a major liver or pancreas operation, there is a chance that one will require a transfusion of blood products (either red blood cells or plasma). This may be necessary during the oper...

Assessment of Insulin Production From Native Pancreas in Patients With Pancreas Transplants

This study will examine whether insulin-producing cells in the pancreas (beta cells) can recover in patients with type 1 diabetes who have had a pancreas transplant. In type 1 diabetes, t...

Relationship Between 18FDG PET/MRI Patterns and ctDNA to Predict HCC Recurrence After Liver Transplantation

Liver transplantation is the standard treatment for patients with early-stage Hepatocellular Carcinoma (HCC). Currently, important treatment decisions, like the selection of patients for t...

Medical and Biotech [MESH] Definitions

A GATA transcription factor that is found predominately in LYMPHOID CELL precursors and has been implicated in the CELL DIFFERENTIATION of HELPER T-CELLS. Haploinsufficiency of GATA3 is associated with HYPOPARATHYROIDISM; SENSORINEURAL HEARING LOSS; and renal anomalies syndrome.

A trace element with atomic symbol Mn, atomic number 25, and atomic weight 54.94. It is concentrated in cell mitochondria, mostly in the pituitary gland, liver, pancreas, kidney, and bone, influences the synthesis of mucopolysaccharides, stimulates hepatic synthesis of cholesterol and fatty acids, and is a cofactor in many enzymes, including arginase and alkaline phosphatase in the liver. (From AMA Drug Evaluations Annual 1992, p2035)

The transference of a pancreas from one human or animal to another.

The major component (about 80%) of the PANCREAS composed of acinar functional units of tubular and spherical cells. The acinar cells synthesize and secrete several digestive enzymes such as TRYPSINOGEN; LIPASE; AMYLASE; and RIBONUCLEASE. Secretion from the exocrine pancreas drains into the pancreatic ductal system and empties into the DUODENUM.

A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas).

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topic

Hepatology
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...


Searches Linking to this Article