Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Exonic knock-out/in gene editing in hematopoietic stem and progenitor cells fully rescues RAG1 immunodeficiency [GUIDE2]

ABSTRACT: Recombination Activating Genes (RAG) are tightly regulated during lymphoid differentiation and their mutations cause a spectrum of severe immunological disorders. Haematopoietic stem/progenitor cell (HSPC) transplantation is the treatment of choice but limited by donor availability and toxicity. To overcome these issues, we developed and validated gene editing (GE) strategies targeting a corrective sequence into the human RAG1 gene by homology-directed repair (HDR). Off-target and RNA-Seq analyses were performed on edited human and patient-derived HSPCs to assesse the genome integrity and the trascriptomic profile. Whereas integration into intron 1 achieved suboptimal levels of correction, in-frame insertion into exon 2 drove faithful recapitulation of physiologic hRAG1 expression and activity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244671 | GEO | 2023/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Exonic knock-out/in gene editing in hematopoietic stem and progenitor cells fully rescues RAG1 immunodeficiency [GUIDE1]

Project description:Recombination Activating Genes (RAG) are tightly regulated during lymphoid differentiation and their mutations cause a spectrum of severe immunological disorders. Haematopoietic stem/progenitor cell (HSPC) transplantation is the treatment of choice but limited by donor availability and toxicity. To overcome these issues, we developed and validated gene editing (GE) strategies targeting a corrective sequence into the human RAG1 gene by homology-directed repair (HDR). Off-target and RNA-Seq analyses were performed on edited human and patient-derived HSPCs to assesse the genome integrity and the trascriptomic profile. Whereas integration into intron 1 achieved suboptimal levels of correction, in-frame insertion into exon 2 drove faithful recapitulation of physiologic hRAG1 expression and activity.

2023-12-31 | GSE244669 | GEO

Exonic knock-out/in gene editing in hematopoietic stem and progenitor cells fully rescues RAG1 immunodeficiency [OFFTARGET]

2023-12-31 | GSE244752 | GEO

Exonic knock-out/in gene editing in hematopoietic stem and progenitor cells fully rescues RAG1 immunodeficiency [RNA-Seq]

2023-12-31 | GSE244672 | GEO

Exonic knock-out/in gene editing in hematopoietic stem and progenitor cells fully rescues RAG1 immunodeficiency

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

2023-12-31 | GSE244753 | GEO

The In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci

Project description:The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo. Here we demonstrate that RAG protein binding occurs in a highly focal manner to a small region of active chromatin encompassing Igκ and Tcrα J gene segments and Igh and Tcrβ J and J-proximal D gene segments. Formation of these small RAG-bound regions, which we refer to as recombination centers, occurs in a developmental stage- and lineage-specific manner. Each RAG protein is independently capable of specific binding within recombination centers. While RAG1 binding is restricted to regions containing recombination signal sequences, RAG2 binds extremely broadly in a pattern that mirrors that of trimethylated lysine 4 of histone 3. We propose that recombination centers coordinate V(D)J recombination by providing discrete sites within which gene segments are captured for recombination.

2010-04-20 | GSE21207 | GEO

The In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci

Project description:The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo. Here we demonstrate that RAG protein binding occurs in a highly focal manner to a small region of active chromatin encompassing IgÎº and TcrÎ± J gene segments and Igh and TcrÎ² J and J-proximal D gene segments. Formation of these small RAG-bound regions, which we refer to as recombination centers, occurs in a developmental stage- and lineage-specific manner. Each RAG protein is independently capable of specific binding within recombination centers. While RAG1 binding is restricted to regions containing recombination signal sequences, RAG2 binds extremely broadly in a pattern that mirrors that of trimethylated lysine 4 of histone 3. We propose that recombination centers coordinate V(D)J recombination by providing discrete sites within which gene segments are captured for recombination. RAG2 binding was analyzed in wild type, RAG2-/-Î², and D708A-RAG1-/-Î² thymocytes. Histone modification H3K4me3 was analyzed in D708A-RAG1-/-Î² and wild type thymocytes.

2010-04-19 | E-GEOD-21207 | biostudies-arrayexpress

Comparing transcriptional profiles of type 2 innate lymphoid cells from WT and Rag1 knockout mice

Project description:Type 2 inflammation contributes to the pathology of skin diseases such as atopic dermatitis and urticaria. Type 2 innate lymphoid cells are key mediators of skin inflammation by releasing type 2 cytokines in response to certain environmental stimuli. We recently found that Rag1 knockout mice exhibit more pronounced skin inflammation in a mouse model of atopic-dermatitis-like disease, despite lacking adaptive immune cells like T helper 2 cells, implicating a critical role of type 2 innate lymphoid cells in this condition. The goal of this study was to characterize transcriptional differences between WT and Rag KO type 2 innate lymphoid cells to determine if Rag knockout leads to cell-intrinsic alterations in innate lymphoid cell function.

2024-05-04 | GSE202232 | GEO

Analysis of difference in transcriptome of ILC2s derived from WT C57BL/6 and RAG1-/- mice

Project description:Purpose: To analyze the transcriptome difference of ILC2s isoalted from WT and RAG-/- mice under inflammaed condition Method: Lung ILC2s from mice chronically challenged with papain (40 µg/20 µl PBS, 6 subsequest papain challenges, day 0, 1, 2, 13, 14, and 15)

2023-01-11 | GSE166779 | GEO

Single nuclei RNA sequencing of skin draining lymph nodes in the setting of skin inflammation and RAG1 fate mapping

Project description:Type 2 inflammation contributes to the pathology of skin diseases such as atopic dermatitis (AD) and urticaria. We previously found that AD-like inflammation induced by calcipotriol in mice is critically mediated by group 2 innate lymphoid cells (ILC2s), while T cells and B cells are dispensable given development of robust AD-like disease in RAG knockout mice. Indeed, we found that in RAG knockout mice AD-like inflammation was worse, with a proportion of ILC2s displaying increased markers of activation. The goal of this study was to characterize transcriptional and epigenomic changes in ILC populations with a history, or not, of expressing RAG1 in the setting of AD-like skin inflammation.

2024-04-28 | GSE192597 | GEO

The role of nitric oxide synthase activity in connection with induced resistance against low-dose hyper-radiosensitivity

Project description:The cells harvested for microarray analysis were high-dose rate (HDR) irradiated, low-dose rate (LDR) irradiated or unirradiated T-47D cells. The HDR-irradiated cells were harvested 24h after a dose of 0.3 Gy at 35 Gy/h, a time where hyper-radiosensitivity (HRS) had returned. The HRS-deficient LDR-irradiated cells were harvested 2 months after a dose of 0.3 Gy at 0.3 Gy/h. LDR-irradiated vs. Control (unirradiated) contains 4 biological replicates. HDR- vs. LDR-irradiated contains 3 biological replicates. HDR-irradiated vs. Control contains 4 biological replicates.

2013-04-15 | E-GEOD-41483 | 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