Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthetic Augmentation of Bilirubin Metabolism in Human Pluripotent Stem Cell-derived Liver Organoids

ABSTRACT: Synthetic Augmentation of Bilirubin Metabolism in Human Pluripotent Stem Cell-derived Liver Organoids

PROVIDER: PRJNA919091 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR23003973_1.fastq.gz	Fastqsanger.gz
	SRR23003973_2.fastq.gz	Fastqsanger.gz
	SRR23003974_1.fastq.gz	Fastqsanger.gz
	SRR23003974_2.fastq.gz	Fastqsanger.gz
	SRR23003975_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

Synthetic augmentation of bilirubin metabolism in human pluripotent stem cell-derived liver organoids.

Project description:UGT1A1 (UDP glucuronosyltransferase family 1 member A1) is the primary enzyme required for bilirubin conjugation, which is essential for preventing hyperbilirubinemia. Animal models lack key human organic anion transporting polypeptides with distinct epigenetic control over bilirubin metabolism, necessitating a human model to interrogate the regulatory mechanism behind UGT1A1 function. Here, we use induced pluripotent stem cells to develop human liver organoids that can emulate conjugation failure phenotype. Bilirubin conjugation assays, chromatin immunoprecipitation, and transcriptome analysis elucidated the role of glucocorticoid antagonism in UGT1A1 activation. This antagonism prevents the binding of transcriptional repressor MECP2 at the expense of NRF2 with associated off-target effects. Therefore, we introduced functional GULO (L-gulonolactone oxidase) in human organoids to augment intracellular ascorbate for NRF2 reactivation. This engineered organoid conjugated more bilirubin and protected against hyperbilirubinemia when transplanted in immunosuppressed Crigler-Najjar syndrome rat model. Collectively, we demonstrate that our organoid system serves as a manipulatable model for interrogating hyperbilirubinemia and potential therapeutic development.

| S-EPMC10679658 | biostudies-literature

Synthetic Augmentation of Bilirubin Metabolism in Human Pluripotent Stem Cell-derived Liver Organoids

Project description:To investigate the efect of perturbation of glucocorticoid signaling on the difference between the biliurbin metabolism in HLOs after treatment with drugs.

2023-10-12 | GSE222362 | GEO

AAV-mediated gene augmentation therapy of CRB1-patient derived retinal organoids restores the histological and transcriptional retinal phenotype

Project description:Retinitis pigmentosa (RP) and Leber congenital amaurosis are inherited retinal dystrophies caused by mutations in, among others, the Crumbs homologue 1 (CRB1) gene. CRB1 is required for organizing apical-basal polarity and adhesion between photoreceptors and Müller glial cells. Using human CRB1 patient induced pluripotent stem cells from RP patients we derived CRB1 retinal organoids, with diminished expression of variant CRB1 protein with immunohistochemical analysis. Single cell RNA-sequencing revealed impact on, among others, the endosomal pathway and cell adhesion and migration in CRB1 patient derived retinal organoids compared to isogenic controls. Adeno-associated viral (AAV) vector-mediated hCRB2 or hCRB1 gene augmentation in Müller glial and photoreceptor cells partially restored the histological and differentially expressed genes phenotype. Altogether, we show proof-of-concept that AAV.hCRB1 or AAV.hCRB2 treatment improved the phenotype of CRB1 patient derived retinal organoids, providing essential information for future gene therapy approaches for patients with mutations in the CRB1 gene.

2023-04-20 | GSE212582 | GEO

Proteome analysis of brainstem organoids from human pluripotent stem cells

Project description:Brain organoids derived from human pluripotent stem cells recapitulate the course of human brain development. We applied proteomic analysis to human brainstem organoids which were developed by a novel method.

2020-05-01 | PXD016807 | JPOST Repository

Retinal organoids with X-linked retinoschisis RS1 (E72K) mutation exhibit a photoreceptor developmental delay and are rescued by gene augmentation therapy

Project description:Background X-linked juvenile retinoschisis (XLRS) is an inherited disease caused by RS1 gene mutation, which leads to retinal splitting and visual impairment. The mechanism of RS1-associated retinal degeneration is not fully understood. Besides, animal models of XLRS have limitations in the study of XLRS. Here, we used human induced pluripotent stem cell (hiPSC)-derived retinal organoids (ROs) to investigate the disease mechanisms and potential treatments for XLRS. Methods hiPSCs reprogrammed from peripheral blood mononuclear cells of two RS1 mutant (E72K) XLRS patients were differentiated into ROs. Subsequently, we explored whether RS1 mutation could affect RO development and explore the effectiveness of RS1 gene augmentation therapy. Results ROs derived from RS1 (E72K) mutation hiPSCs exhibited a developmental delay in the photoreceptor, retinoschisin (RS1) deficiency, and altered spontaneous activity compared with control ROs. Furthermore, the delays in development were associated with decreased expression of rod-specific precursor markers (NRL) and photoreceptor-specific markers (RCVRN). Adeno-associated virus (AAV)-mediated gene augmentation with RS1 at the photoreceptor immature stage rescued the rod photoreceptor developmental delay in ROs with the RS1 (E72K) mutation. Conclusions The RS1 (E72K) mutation results in the photoreceptor development delay in ROs and can be partially rescued by the RS1 gene augmentation therapy.

2024-05-17 | GSE267405 | GEO

Combination of a microfluidic device with brain extracellular matrix promotes structural and functional maturation of human brain organoids

Project description:Brain organoids derived from human pluripotent stem cells provide a highly valuable in vitro model to recapitulate human brain development and neurological diseases. However, the current systems for brain organoid culture require further improvement for the reliable production of high-quality organoids. Here, we demonstrate two engineering elements to improve human brain organoid culture, (1) a human brain extracellular matrix (BEM) to provide brain-specific cues and (2) a microfluidic device with periodic flow to improve the survival and reduce the variability of organoids. A three-dimensional culture modified with BEM significantly enhanced neurogenesis in developing brain organoids from human induced pluripotent stem cells. Cortical layer development, volumetric augmentation, and electrophysiological function of human brain organoids were further improved in a reproducible manner by dynamic culture in microfluidic chamber devices. Our engineering concept of reconstituting brain-mimetic microenvironments facilitates the development of a reliable culture platform for brain organoids, enabling effective modeling and drug development for human brain diseases.

2021-06-02 | PXD025397 | Pride

Proteomics characterisation of induced pluripotent stem cells and cortical brain organoids.

Project description:A method was developed to reproducibly produce neural retina and cortical brain regions from confluent cultures of stem cells. The spontaneously generated cortical organoids were isolated and cultured in suspension conditions for maturation. Proteomic analysis of both the original induced pluripotent stem cells and the cortical organoids demonstrated the increased presence of synaptic components, indicating maturity.

2022-05-06 | PXD025933 | Pride

Modeling PRPF31 retinitis pigmentosa using iPSC-derived retinal organoids and retinal pigmented epithelium and rescue by gene augmentation strategy

Project description:Mutations in the ubiquitously expressed pre-mRNA processing factor (PRPF) 31, one of the most common cause of dominant form of Retinitis Pigmentosa (RP), lead to retina-specific phenotype. It is uncertain which retinal cell types are affected and animal models do not clearly present the RP phenotype observed in PRPF31 patients. Retinal organoids and retinal pigmented epithelial (RPE) cells derived from human induced pluripotent stem cells (iPSCs) provide potential opportunities for studying human PRPF31-related RP. We demonstrated that RPE cells carrying PRPF31 mutations present important morphological and functional changes and that PRPF31-mutated retinal organoids recapitulate the human RP phenotype, with a rod photoreceptor cell death followed by a loss of cones. The low level of PRPF31 expression may explain the defective phenotypes of PRPF31-mutated RPE and photoreceptor cells, which were not observed in cells derived from asymptomatic patients or after correction of the pathogenic mutation by CRISPR/Cas9. Transcriptome profiles revealed differentially expressed and mis-spliced genes belonging to pathways in line with the observed defective phenotypes. The rescue of RPE and photoreceptor defective phenotypes by PRPF31 gene augmentation, provide the proof of concept for future therapeutic strategies.

2022-08-01 | GSE206529 | GEO

Modelling Plasticity and Dysplasia of Pancreatic Ductal Organoids Derived from Human Pluripotent Stem Cells

Project description:Full protein measurements from in vitro differentiation of the human embryonic stem cell line HUES8 into pancreatic progenitors (PP) and pancreatic duct-like organoids (PDLOs). Protein intensities were quantified by mass spectrometry analysis from PPs at day 13 and from PDLOs at day 59. Please see related publication “Modelling Plasticity and Dysplasia of Pancreatic Ductal Organoids Derived from Human Pluripotent Stem Cells” for experimental details.

2021-03-19 | PXD018785 | Pride

Self-Organized Generation Of Hepatic Cord Like Organoids (HCLOs) With Zonal Diversity (ChIPseq)

Project description:To investigate the efect of extracellular bilirubin and intracellular ascorbate on the development of zonal hepatocytes in human liver organoids.

2024-09-18 | GSE222653 | GEO

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