Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A cellular disease model towards gene therapy of TGM1-dependent Lamellar Ichthyosis

ABSTRACT: A cellular disease model towards gene therapy of TGM1-dependent Lamellar Ichthyosis

PROVIDER: PRJNA1116216 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR29165138_1.fastq.gz	Fastqsanger.gz
	SRR29165138_2.fastq.gz	Fastqsanger.gz
	SRR29165139_1.fastq.gz	Fastqsanger.gz
	SRR29165139_2.fastq.gz	Fastqsanger.gz
	SRR29165140.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 5

Similar Datasets

A cellular disease model towards gene therapy of TGM1-dependent Lamellar Ichthyosis

Project description:Lamellar Ichthyosis (LI) is a chronic disease, mostly caused by mutations in TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene edited cells showed complete absence of Transglutaminase-1 (TG1) expression and recapitulate a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro. Using a SINγ-RV vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1-null keratinocytes displayed proper TG1 expression, enzymatic activity and cornified envelopes formation, hence restored proper epidermal architecture. Single cell multiomic analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial to epidermal regeneration. This study serves as a proof-of-concept for assessing the potential of this therapeutic approach in treating TGM1 dependent LI.

2024-07-29 | GSE268321 | GEO

Transcriptomic Analysis of the Major Orphan Ichthyosis Subtypes Reveals Shared Immune and Barrier Signatures

Project description:In this study we performed the first global RNA-seq analysis in 54 ichthyosis patients (7 Netherton syndrome/NS, 13 epidermolytic ichthyosis/EI, 16 lamellar ichthyosis/LI, 18 congenital ichthyosiform erythroderma/CIE) and 40 healthy controls. Differentially expressed genes (DEGs) were defined based on fold changes/FCH>2 and false discovery rate/FDR<0.05 criteria. We found robust and significant Th22/Th17 skewing in all subtypes (e.g. IL-17A/C/F, S100A7/8/9/12; p<0.001) with modest changes in Th2 pathway, primarily in NS, and Th1 skewing in CIE.

2022-03-06 | GSE192832 | GEO

Modeling Phenotypic Heterogeneity Towards Evolutionary Inspired Osteosarcoma Therapy

Project description:Modeling Phenotypic Heterogeneity Towards Evolutionary Inspired Osteosarcoma Therapy

| PRJNA1003084 | ENA

Towards minimal residual disease-directed therapy in melanoma

Project description:Towards minimal residual disease-directed therapy in melanoma

| PRJNA477841 | ENA

A cellular disease model toward gene therapy of TGM1-dependent lamellar ichthyosis.

Project description:Lamellar ichthyosis (LI) is a chronic disease, mostly caused by mutations in the TGM1 gene, marked by impaired skin barrier formation. No definitive therapies are available, and current treatments aim at symptomatic relief. LI mouse models often fail to faithfully replicate the clinical and histopathological features of human skin conditions. To develop advanced therapeutic approaches, such as combined ex vivo cell and gene therapy, we established a human cellular model of LI by efficient CRISPR-Cas9-mediated gene ablation of the TGM1 gene in human primary clonogenic keratinocytes. Gene-edited cells showed complete absence of transglutaminase 1 (TG1) expression and recapitulated a hyperkeratotic phenotype with most of the molecular hallmarks of LI in vitro. Using a self-inactivating γ-retroviral (SINγ-RV) vector expressing transgenic TGM1 under the control of its own promoter, we tested an ex vivo gene therapy approach and validate the model of LI as a platform for pre-clinical evaluation studies. Gene-corrected TGM1-null keratinocytes displayed proper TG1 expression, enzymatic activity, and cornified envelope formation and, hence, restored proper epidermal architecture. Single-cell multiomics analysis demonstrated proviral integrations in holoclone-forming epidermal stem cells, which are crucial for epidermal regeneration. This study serves as a proof of concept for assessing the potential of this therapeutic approach in treating TGM1-dependent LI.

| S-EPMC11372595 | biostudies-literature

Ichthyosis molecular fingerprinting shows profound Th17-skewing and a unique barrier genomic signature

Project description:The purpose of this study was to analyze the genomic signatures and profiles of skin from ichthyosis (various subtypes) vs. healthy patients. The analysis strategy was to study differentially expressed genes common to the ichthyosis shared phenotype, as well as individual ichthyosis subtypes, and compare and contrast to the genomic profiles of atopic dermatitis and psoriasis.

2018-10-10 | GSE108640 | GEO

Towards phage therapy against multi-drug resistant Klebsiella pneumoniae

Project description:Towards phage therapy against multi-drug resistant Klebsiella pneumoniae

| PRJEB56576 | ENA

Skin and stool microbiome in patients with ichthyosis

Project description:Skin microbiome ichthyosis

| PRJEB60267 | ENA

KDM5B links cellular transcriptome heterogeneity to therapy resistance

Project description:KDM5B links cellular transcriptome heterogeneity to therapy resistance

| PRJNA414335 | ENA

Functional multiomics of cellular therapy and immune checkpoint blockade therapy for solid tumors

Project description:Functional multiomics of cellular therapy and immune checkpoint blockade therapy for solid tumors