Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell analysis of human fetal and post-natal γδ thymocytes reveals distinct functional programming.

ABSTRACT: Developmental thymic waves of innate-like and adaptive-like gd T cells have been described, but the current understanding of γδ T cell development is mainly limited to mouse models. Here, we combined single cell (sc) RNA gene expression and sc γδ T cell receptor (TCR) sequencing on fetal and pediatric γδ thymocytes in order to understand the ontogeny of human γδ T cells. Mature fetal γδ thymocytes were committed to either a type 1, a type 3 or type 2-like effector fate, independent from γδ T cell subset type (Vγ9Vδ2 vs nonVγ9Vδ2), and were enriched for public CDR3 features upon maturation. Strikingly, type 1, type 3 and type 2 cells expressed different CDR3 sequences and followed distinct developmental trajectories. In contrast, the pediatric thymus generated only a small effector subset that was highly biased towards Vγ9Vδ2 TCR usage and showed a mixed type 1/type 3 effector profile. Thus, our combined dataset of gene expression and detailed TCR information at the single-cell level defines γδ thymocyte development in human and provides a resource for further study.

ORGANISM(S): Homo sapiens

PROVIDER: GSE180059 | GEO | 2022/08/19

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

The human fetal thymus generates effector invariant γδ T cells in a Lin28b-dependent manner

Project description:In the mouse thymus, invariant γδ T cells are generated at well-defined times during development and acquire effector functions before exiting the thymus. However, whether such thymic programming can occur in human is not known. Here we analyzed human fetal and post-natal γδ thymocytes and investigated the role of hematopoietic-stem-and-precursor-cells (HSPC) in the generation of human γδ T cells. Unlike post-natal γδ thymocytes, fetal γδ thymocytes were functionally programmed (e.g. IFNγ, granzymes), expressed low levels of terminal-deoxynucleotidyl-transferase (TdT) and were highly enriched for invariant/public germline-encoded CDR3 sequences (TRGV8-TRJP1-CATWDTTGWFKIF, TRDV2-TRDD3-CACDTGGY and TRDV1-TRDD3-CALGELGD, previously shown to be expanded in cytomegalovirus infection) composed of short-homology-repeat-containing gene segments. Furthermore, these unique characteristics were due to an intrinsic property of fetal HSPC caused by high expression of the RNA-binding protein Lin28b. In conclusion, our data indicate that the human fetal thymus generates, in a HSPC/Lin28b-dependent manner, invariant γδ T cells with programmed effector functions.

2019-11-21 | GSE128163 | GEO

RNA Sequencing of Fetal and Adult Mature Thymic Vγ1+ γδ T-Cells

Project description:γδ T-cells form an integral arm of the immune system through their rapid and potent effector functions, and are critical players during both protective and destructive immunity. However, the factors that dictate γδ T-cell functional programming in vivo remain to be fully elucidated. Here, we employed RBPJ-inducible and KN6-transgenic mice to assess the roles of ontogenic timing, T-cell receptor (TCR) signal strength, and Notch signaling in the generation of γδ T-cell functional subsets in vivo. We found skewed generation of Vγ1+ cells toward the PLZF+ γδ T-cell lineage at the fetal stage. Similarly, generation of interleukin (IL)-17 producing γδ T-cells was favored during, although not exclusive to, the fetal stage. Strong TCR signals, in conjunction with Notch, were necessary for the generation of IL-4 producing γδ T-cells. Conversely, weak TCR signals were amenable for the generation of IL-17 producing γδ T-cells, which was Notch-independent. Additionally and surprisingly, Notch signaling was also dispensable for peripheral γδ T-cell IL-17 production. Thus, our results precisely defined the roles of ontogenic timing, TCR signal strength, and Notch signaling in γδ T-cell functional programming in vivo.

2021-05-01 | GSE166086 | GEO

Single-Cell RNA Sequencing of Thymic KN6 γδ T-Cells Modulated by TCR Signal Strength and Notch Signaling

2021-05-01 | GSE165908 | GEO

Murine KN6-Lig+ and Lig- DN4 Cells compared to DN3 cells

Project description:Transcriptomic profiling of KN6 DN4 TCR Tg thymocytes adopting the γδ fate (Lig+) or the αβ fate (Lig-)

2014-12-02 | GSE63730 | GEO

Single cell RNA-seq reveals high heterogeneity among human γδ T cells.

Project description:Human γδ T cells take a small but important part in the immune system. Human γδ T cells are usually categorized by the V gene of their T cell receptor (TCR) δ chain; most of which are Vδ1+ or Vδ2+. Naive γδ T cells are often found from neonates and cytotoxic γδ T cells (γδCTLs) are frequent in adults. However, phenotypes and the developmental programs of human γδ T cells are not fully clear. Here, by single-cell RNA sequencing (sc-RNAseq) of transcriptome and T cell receptor (sc-TCRseq) on γδ T cells from neonates and adults, we revealed human γδ T cells can be divided as naïve T cells, γδCTLs, and γδNKT cells which are featured by pro-Vδ1, Vδ1, and Vδ2 TCR repertoire, respectively. γδNKT cells can be further described as γδNKT-1, γδNKT-2, and γδNKT-17 cells.

2020-07-31 | GSE149356 | GEO

Butyrophilin 3A1 binds phosphorylated antigens and stimulates human TCR γδ cells.

Project description:We used genetic approaches to identify butyrophilin 3A1 (BTN3A1) as the molecule that binds and presents phosphorylated antigens to Vγ9Vδ2 TCR–expressing cells. BTN3A1 represents a novel antigen–presenting molecule for the activation of Vγ9Vδ2 TCR–expressing cells which play important roles in human tumor immunity and host defense.

2012-10-01 | GSE37634 | GEO

γδ-T cells and αβ-TCR transduced γδ-T cells

Project description:RNA expression of unstimulated γδ-T cells,γδ-TCR-stimulated γδ-T cells, unstimulated αβ-TCR transduced γδ-T cells and αβ-TCR-stimulated αβ-TCR transduced γδ-T cells.

2023-09-07 | GSE216880 | GEO

TCR signal strength controls thymic differentiation of discrete proinflammatory γδT cell subsetsistinct TCR signal strength requirements in the thymus

Project description:The murine thymus produces discrete γδ T cell subsets making either IFN-γ or IL-17, but the role of the TCR in this developmental process remains controversial. Here we generated a non-transgenic and polyclonal model of reduced TCR expression and signal strength selectively on γδ T cells. Mice haploinsufficient for both CD3γ and CD3δ (CD3DH) showed normal αβ thymocyte subsets but specific defects in γδ T cell development, namely impaired differentiation of IL-17-producing embryonic Vγ6+ (but not adult Vγ4+) γδ T cells and a marked depletion of IFN-γ-producing CD122+ NK1.1+ (Vγ1-biased) γδ T cells throughout life. As result, adult CD3DH mice showed defective peripheral IFN-γ responses and were resistant to experimental cerebral malaria. Thus, strong TCR signaling is required within specific developmental windows with distinct Vγ usage and differential cytokine production by effector γδ T cell subsets.

2016-03-29 | GSE71637 | GEO

Genomic and functional studies in T-Acute Lymphoblastic Leukemia patients exhibiting clonal T Cell Receptor γ and δ gene rearrangement

Project description:T-cell Acute Lymphoblastic Leukemia (T-ALL) is a lymphoid malignancy characterized by clonal proliferation of immature thymocytes arrested at particular stage of differentiation. Earlier studies from our lab have demonstrated that 30% of Indian T-ALL patients exhibited clonal rearrangement of both TCR γ and δ genes. The survival was higher in T-ALL patients showing clonal rearrangements for TCR γ and δ genes. In the present study, we aimed at investigating the gene expression profiles of TCR γδ+ T-ALL patients and correlating it with functional analysis to understand the reasons for increased survival in these patients. Our studies demonstrate differential expression of genes in TCR γδ clonal T-ALL compared to non TCR γδ clonal T-ALL patients. Functional annotation of significantly upregulated genes (p<0.05) in TCR γδ+ T-ALL patients showed involvement in antigen processing and presentation, cell-cell communication, apoptosis, cell adhesion molecules and immune synapse pathways. Expression of eight selected genes (SMAD3, NFkB1, HLA-DQB1, SOCS2, CISH, FASLG, RXRA,and IFNβ1) was validated in TCRαβ+ and TCRγδ+ subgroups of T-ALL patients using quantitative Real-time PCR. Studies focusing on functional aspects of the gene(s) identified from gene expression profile would aid in developing future therapeutic strategies.

2016-04-25 | GSE37389 | GEO

CD117, CD200 and CD371 identifies seven populations of γδ thymocytes programmed towards three distinct effector subsets in adult mice

Project description:Murine γδ T cells include several effector subsets that fulfil distinct functional roles. In pathological conditions, such as cancer, some γδ T cell subsets are highly protective whereas other subsets may exacerbate disease. γδ T cells are programmed for their effector function during their development in the thymus. Investigations of γδ T cell development have been hampered by the scarcity of surface markers distinguishing different development stages. In this study, we found that addition of CD117, CD200 and CD371 to existing markers, allowed identification of seven distinct development stages (named A, B, C, D, E, F and G) present in both the Vγ1.1+ and Vγ2+ thymocyte subsets. We provide evidence for the existence of three distinct pathways leading to export of γδ T cells, two of which express high levels of CD24. These pathways are dominated by different TCRδ repertoires shaped by TCR signalling or lack thereof. Each pathway express distinct cytokine and transcription factor profiles associated with γδT1, γδNKT and adaptive γδ T cells. Thus, the identification of additional γδ T cell development stages in this study connects three distinct development pathways to the programming of three γδ T cell effector subsets.

2017-10-18 | GSE97137 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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