Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Thymic epithelial cell alterations and defective thymopoiesis lead to central and peripheral tolerance perturbation in MHCII deficiency

ABSTRACT: Thymic epithelial cell alterations and defective thymopoiesis lead to central and peripheral tolerance perturbation in MHCII deficiency

PROVIDER: PRJNA701010 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR13668414_1.fastq.gz	Fastqsanger.gz
	SRR13668414_2.fastq.gz	Fastqsanger.gz
	SRR13668415_1.fastq.gz	Fastqsanger.gz
	SRR13668415_2.fastq.gz	Fastqsanger.gz
	SRR13668416_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 24

Similar Datasets

Thymic epithelial cell alterations and defective thymopoiesis lead to central and peripheral tolerance perturbation in MHCII deficiency

Project description:Major Histocompatibility Complex (MHC) class II (MHCII) deficiency, also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules. MHCII deficiency results in impaired cellular and humoral immune responses, leading to severe infections and autoimmunity. The contribution of thymic epithelial cell (TEC) defects to the pathogenesis of this primary immunodeficiency has not been well characterized to date, in particular in regard to immune dysregulation. To this aim, we have performed an in-depth cellular and molecular characterization of TEC alterations in this disease. We observed an overall perturbation of thymic structure and function in both MHCII-/- mice and patients. Transcriptomic and proteomic profiling of murine TEC revealed several alterations. In particular, in MHCII-/- mice, impaired cross-talk and mTEC maturation resulted in altered promiscuous gene expression and leaky central tolerance. Furthermore, we observed peripheral tolerance impairment, likely due to defective Treg cell generation and/or function and B cell tolerance breakdown. Overall, our findings reveal disease-specific TEC defects resulting in perturbation of central tolerance and limiting the potential effect of hematopoietic stem cell transplantation in MHCII deficiency.

2022-01-28 | GSE166463 | GEO

Thymic Epithelial Cell Alterations and Defective Thymopoiesis Lead to Central and Peripheral Tolerance Perturbation in MHCII Deficiency.

Project description:Major Histocompatibility Complex (MHC) class II (MHCII) deficiency (MHCII-D), also known as Bare Lymphocyte Syndrome (BLS), is a rare combined immunodeficiency due to mutations in genes regulating expression of MHCII molecules. MHCII deficiency results in impaired cellular and humoral immune responses, leading to severe infections and autoimmunity. Abnormal cross-talk with developing T cells due to the absence of MHCII expression likely leads to defects in thymic epithelial cells (TEC). However, the contribution of TEC alterations to the pathogenesis of this primary immunodeficiency has not been well characterized to date, in particular in regard to immune dysregulation. To this aim, we have performed an in-depth cellular and molecular characterization of TEC in this disease. We observed an overall perturbation of thymic structure and function in both MHCII-/- mice and patients. Transcriptomic and proteomic profiling of murine TEC revealed several alterations. In particular, we demonstrated that impairment of lymphostromal cross-talk in the thymus of MHCII-/- mice affects mTEC maturation and promiscuous gene expression and causes defects of central tolerance. Furthermore, we observed peripheral tolerance impairment, likely due to defective Treg cell generation and/or function and B cell tolerance breakdown. Overall, our findings reveal disease-specific TEC defects resulting in perturbation of central tolerance and limiting the potential benefits of hematopoietic stem cell transplantation in MHCII deficiency.

| S-EPMC8239840 | biostudies-literature

Transcriptome data of MHCII-high and MHCII-low hematopoietic stem cells of middle-aged mice

Project description:Analysis of MHCII-high (MHCII-hi) and MHCII-low (MHCII-lo) hematopoietic stem cells (Lineage-Sca-1+c-Kit+CD150+Flt3-CD48-). The two population of hematopoietic stem cell (HSC) were purified from the bone marrow of 12 months old (12 mo) mice. Results provide insight into the role of MHCII in HSC.

2023-08-08 | GSE211206 | GEO

Transcriptome data of MHCII-high and MHCII-low hematopoietic stem cells of mice under homeostasis

Project description:Analysis of MHCII-high (MHCII-hi) and MHCII-low (MHCII-lo) hematopoietic stem cells (Lineage-Sca-1+c-Kit+CD150+Flt3-CD48-). The two population of hematopoietic stem cell (HSC) were purified from the bone marrow of 5 months old WT mice (Ctrl). Results provide insight into the role of MHCII in HSC.

2023-08-08 | GSE211203 | GEO

A single cell analysis of porcine thymopoiesis and thymic iNKT cells

Project description:Many aspects of the porcine immune system remain poorly characterized which poses a barrier to improving swine health and utilizing pigs as preclinical models. Here, we employed single-cell RNA sequencing (scRNA-seq) to create a cell atlas of the postnatal pig thymus. Our data found conserved features as well as species-specific differences in cell states and cell types compared to human thymocytes. We also describe several unconventional T cell types with gene expression profiles associated with innate effector functions. This includes a cell census of >11,000 differentiating invariant natural killer T (iNKT) cells, which revealed that the functional diversity of pig iNKT cells differs substantially from the paradigm of iNKT0/1/2/17 subset differentiation established in mice. Collectively, our data characterizes key differentiation events in porcine thymopoiesis and iNKT cell maturation, which provide new insights into pig T cell development.

2022-08-04 | GSE192520 | GEO

Transcriptome data of MHCII-high and MHCII-low hematopoietic stem cells of mice exposed to irradiation

Project description:Analysis of MHCII-high (MHCII-hi) and MHCII-low (MHCII-lo) hematopoietic stem cells (Lineage-Sca-1+c-Kit+CD150+Flt3-CD48-). The two population of hematopoietic stem cell (HSC) were purified from the bone marrow of mice at 3 months post 5 Gy total body irradiation (IR). Results provide insight into the role of MHCII in HSC.

2023-08-08 | GSE211205 | GEO

A single cell analysis of porcine thymopoiesis and thymic iNKT cells

Project description:A single cell analysis of porcine thymopoiesis and thymic iNKT cells

| PRJNA791835 | ENA

Recapitulation of murine thymopoiesis in vitro from single hematopoietic stem cells

Project description:We report a serum-free, 3-D murine artificial thymic organoid (ATO) system that mimics normal murine thymopoiesis from four different mouse strains with the production of all T cell populations, from early thymic progenitors to functional single positive (CD8SP and CD4SP) TCRaband TCRyd cells. RNA sequencing aligned ATO-derived populations with phenotypically identical primary thymocytes. ATOs initiated with Rag1-/- marrow produced the same differentiation block as seen in the endogenous thymus, and Notch signaling patterns in ATOs mirrored primary thymopoiesis. ATOs initiated with defined hematopoietic stem cells (HSCs) and progenitors from marrow and thymus recapitulated subsequent stages and the normal kinetics of T cell differentiation. Remarkably, a single HSC deposited into ATOs generated a complete trajectory of T cell differentiation producing a similar diverse TCR repertoire across clones. ATOs represent a technically simple, highly reproducible and powerful experimental platform for the study of clonal thymopoiesis from HSCs.

2020-12-15 | GSE146224 | GEO

Transcriptome data of MHCII-high and MHCII-low hematopoietic stem cells of mice

Project description:Transcriptome data of MHCII-high and MHCII-low hematopoietic stem cells of mice

| PRJNA869547 | ENA

T cell progenitor therapy-facilitated thymopoiesis depends upon thymic input and continued thymic microenvironment interaction.

Project description:Infusion of in vitro-derived T cell progenitor (proT) therapy with hematopoietic stem cell transplant aids the recovery of the thymus damaged by total body irradiation. To understand the interaction between proTs and the thymic microenvironment, WT mice were lethally irradiated and given T cell-deficient (Rag1-/-) marrow with WT in vitro-generated proTs, limiting mature T cell development to infused proTs. ProTs within the host thymus led to a significant increase in thymic epithelial cells (TECs) by day 21 after transplant, increasing actively cycling TECs. Upon thymus egress (day 28), proT TEC effects were lost, suggesting that continued signaling from proTs is required to sustain TEC cycling and cellularity. Thymocytes increased significantly by day 21, followed by a significant improvement in mature T cell numbers in the periphery by day 35. This protective surge was temporary, receding by day 60. Double-negative 2 (DN2) proTs selectively increased thymocyte number, while DN3 proTs preferentially increased TECs and T cells in the spleen that persisted at day 60. These findings highlight the importance of the interaction between proTs and TECs in the proliferation and survival of TECs and that the maturation stage of proTs has unique effects on thymopoiesis and peripheral T cell recovery.

| S-EPMC5436538 | 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