Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Formation and fate of stem-cell like Tcf7+ CD8+ T cells during a primary immune response to viral infection [scRNA-seq]

ABSTRACT: In response to infection, naïve CD8+ T cells (Tn) expand and differentiate into short-lived terminal effector (Tte) cells, which eliminate infected cells, or into central memory (Tcm) cells, which persist following pathogen clearance and mediate protection against re-infection thanks to their stem cell-like properties. The stage-specific signals required for the cell fate changes have remained incompletely understood. Here we find that Tn cells, which express the transcription factor Tcf1 (Tcf7), yield Tcf1+ cells, which retain stem-like potential throughout the primary response and which quantitatively yield Tcf1+ Tcm cells following pathogen clearance. However, only the Tcf1+ cells present during priming are competent to yield Tcf1- Tte cells. Priming commits cells to undergo multiple divisions while maintaining Tcf1 expression. The presence of type I interferon during the division, rather than the priming phase suppresses Tcf1 expression. Tcf1 loss results in the stable loss of stemness, an event that precedes the stable acquisition of a Tte state. Thus, inflammatory cytokines drive Tte differentiation from dividing Tcf1+ cells, which are prone to become Tcm cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE221968 | GEO | 2023/11/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Formation and fate of stem-cell like Tcf7+ CD8+ T cells during a primary immune response to viral infection [ATAC-seq]

Project description:In response to infection, naïve CD8+ T cells (Tn) expand and differentiate into short-lived terminal effector (Tte) cells, which eliminate infected cells, or into central memory (Tcm) cells, which persist following pathogen clearance and mediate protection against re-infection thanks to their stem cell-like properties. The stage-specific signals required for the cell fate changes have remained incompletely understood. Here we find that Tn cells, which express the transcription factor Tcf1 (Tcf7), yield Tcf1+ cells, which retain stem-like potential throughout the primary response and which quantitatively yield Tcf1+ Tcm cells following pathogen clearance. However, only the Tcf1+ cells present during priming are competent to yield Tcf1- Tte cells. Priming commits cells to undergo multiple divisions while maintaining Tcf1 expression. The presence of type I interferon during the division, rather than the priming phase suppresses Tcf1 expression. Tcf1 loss results in the stable loss of stemness, an event that precedes the stable acquisition of a Tte state. Thus, inflammatory cytokines drive Tte differentiation from dividing Tcf1+ cells, which are prone to become Tcm cells.

2023-11-06 | GSE221967 | GEO

Acute CD8+ T cell responses to viral infection harbor Tcf1-dependent stem-like cells that quantitatively yield central memory [ATAC-seq]

Project description:Central memory CD8+ T cells (TCM) can protect from secondary pathogen infection, from chronic infection and cancer as a result of their stem cell-like properties. However, the developmental origin of central memory cells and consequently the basis of their stemness have not been resolved. By monitoring the expression of the transcription factor Tcf1 (Tcf7), which is essential for central memory formation, we identified a small subset of CD8+ T cells present during the acute response to primary infection. These cells lacked cytotoxic effector function, resembled TCM both transcriptionally and epigenetically, had stem cell-like properties, and quantitatively yielded TCM. Stemness effector phase Tcf7+ CD8+ T cells depended on Tcf1 protein expression and on a set of Tcf1-dependent genes associated with adult stem cells. Stemness was thus not acquired subsequent to antigen clearance but was maintained in rare CD8+ T cells responding to acute infection and these cells quantitatively yielded TCM.

2020-10-30 | GSE144382 | GEO

Acute CD8+ T cell responses to viral infection harbor Tcf1-dependent stem-like cells that quantitatively yield central memory [RNA-seq]

2020-10-30 | GSE142409 | GEO

Gene expressions of CD4+ T cells in each developmental stages

Project description:The development of T cells has been characterized as taking place over three stages: naïve (Tn), central memory (Tcm), and effector memory (Tem) cells. Recently, stem cell memory T cells (Tscm) were found to be the least-developed memory subset. We performed detailed analysis of the gene expression of human CD4+ T cells with clear distinction of the Tn, Tscm, Tcm, and Tem stages. We sorted Tn, Tscm, Tcm, and Tem CD4+ T cells from the peripheral blood of six healthy volunteers to see the differences of gene expression between each developmental stage.

2015-05-12 | E-GEOD-61697 | biostudies-arrayexpress

Tcf1 preprograms glycolysis mobilization in central memory CD8+ T cells in recall response

Project description:The goal of this study is to determine the impact of Tcf1 deficiency on recall capacity of central memory CD8+ T (Tcm) cells. We demonstrate that loss of Tcf1 shows limited impact on Tcm cells at resting state, but severely comprimises activation of glycolysis and other key regulators during recall response. Based on these findings, we propose that Tcf1 preprograms the responsiveness of Tcm cells to secondary challenges.

2021-11-10 | GSE177064 | GEO

Gene expressions of CD4+ T cells in each developmental stages

2015-05-12 | GSE61697 | GEO

Gene expressions of CD4+ T cells from patients with rheumatoid arthritis in each developmental stages

Project description:The development of T cells has been characterized as taking place over three stages: naïve (Tn), central memory (Tcm), and effector memory (Tem) cells. Recently, stem cell memory T cells (Tscm) were found to be the least-developed memory subset. We performed detailed analysis of the gene expression of human CD4+ T cells from patients with rheumatoid arthritis with clear distinction of the Tn, Tscm, Tcm, and Tem stages.

2021-04-01 | GSE80785 | GEO

Transcription profiling of human CD8 naive (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells

Project description:Memory T cells are heterogeneous in terms of their phenotype and functional properties. We investigated the molecular profiles of human CD8 naïve (TN), central memory (TCM), effector memory (TEM), and effector memory RA (TEMRA) T cells using gene expression microarrays and phospho-protein-specific intracellular flow cytometry. We demonstrate that TCM have a gene expression and cytokine signaling signature that lies between that of TN and TEM or TEMRA cells, whereas TEM and TEMRA are closely related. Our data define the molecular basis for the different functional properties of central and effector memory subsets. We show that TEM and TEMRA cells strongly express genes with known importance in CD8 T cell effector function. In contrast, TCM are characterized by high basal and cytokine-induced STAT5 phosphorylation, reflecting their capacity for self-renewal. Altogether, our results distinguish TCM and TEM/TEMRA at the molecular level and are consistent with the concept that TCM represent memory stem cells.

2005-01-01 | E-TABM-40 | biostudies-arrayexpress

IL-7 and IL-15 instruct the generation of human memory stem T cells from naïve precursors

Project description:The identification of the most appropriate T-cell subset to ensure optimal persistence and anti-tumor activity is a major goal of cancer immunotherapy. We identified a novel post-mitotic CD45RA+CD62L+ T cell subpopulation (TTN), generated in vitro upon activation of naïve T (TN) cells with beads conjugated to anti-CD3 and anti-CD28 antibodies. This cell population is highly proliferative, produces low levels of IFNg and cytotoxic molecules, and requires IL-7 and IL-15 for in vitro expansion. To investigate whether this cell population represents a novel T-cell subset, we compared the transcriptomic profile of TTN with that of other T-cell subsets, namely naturally occurring TN and central memory (TCM) and manipulated cells of TCM origin (TTCM). We collected RNA from unmanipulated purified T-cell subsets (TN and TCM) or from T-cell subsets that were in vitro activated and transduced (TTN and TTCM). In vitro generated subsets were kept in culture for 15 days after activation before harvesting. Samples were then processed for total RNA extraction and hybridization on Affymetrix microarrays. Three biological replicas (A, B, C) were used for each of the 4 conditions (1: TN; 2: TCM; 3: TTN; 4: TTCM) for a total of 12 samples.

2012-11-16 | E-GEOD-41909 | biostudies-arrayexpress

Memory CD8+ T cells induce precocious effector differentiation of naive T cells through quorum sensing-like behavior

Project description:Some unicellular organisms exhibit collective decision-making through intercellular communication once a quorum of members sense an environmental stress. Whether T cells at different states of differentiation may also synchronize their behavior on a population basis through direct interactions remains unclear. We report that memory CD8+ T cells (TMem) directly interact with naive T cells (TN) during priming, affecting the phenotypic, functional, transcriptional and metabolic differentiation of TN-derived progeny. This previously unrecognized, contact and concentration-dependent interaction between naive (TN) and memory CD8+ T cells (TMem) directly enhanced TN effector differentiation through non-apoptotic Fas signaling resulting in downstream Akt pathway activation. TN primed with TMem exhibited significantly impaired persistence and antitumor activity compared with TN primed alone. Disruption of FasL-Fas signaling in TN cells limited differentiation and enhanced anti-tumor immunity while provision of exogenous FasL in the absence of TMem impaired anti-tumor immunity by augmenting TN differentiation. These findings reveal that the full therapeutic potential of TN-derived cells for adoptive immunotherapy requires physical separation from TMem prior to priming or antagonism of Fas-signaling.

2015-03-01 | GSE56344 | 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