Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional basis of mouse and human dendritic cell heterogeneity revealed by single-cell profiling

ABSTRACT: Dendritic cells (DCs) play a critical role in orchestrating adaptive immune responses due to their unique ability to serve as a principal antigen-presenting cell type capable of initiating T cell responses. Classical dendritic cells have been divided into two subsets, cDC1 and cDC2, based on phenotypic markers and their distinct abilities to prime CD8 and CD4 T cells and direct their differentiation into effectors. Whilst the transcriptional features of the cDC1 subset have been well characterized, the heterogeneity of cDC2 and the development and function of distinct cell types comprising this subset remain poorly understood. Unbiased single-cell RNA sequencing analysis of DCs, combined with genetic reporter expression and fate-mapping revealed two principal cDC2 lineages, their developmental pathways and transcriptional regulators, including the expression of T-bet and RORt, two key transcription factors known to define functional adaptive and innate lymphocyte subsets. The cDC2 lineages were characterized by distinct metabolic and functional programs with phenotypic conservation observed across tissues. Extending the findings in mice to humans revealed conserved characteristics of DC heterogeneity and the presence of the newly defined DC subsets in human autoimmune disease and cancer.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE137710 | GEO | 2019/10/25

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Progenitors of distinct lineages shape the diversity of mature type 2 conventional dendritic cells.

Project description:Conventional Dendritic Cells (cDC) are antigen-presenting cells comprising cDC1 and cDC2 subsets, responsible for priming naïve CD8+ and CD4+ T cells, respectively. Recent studies have unveiled cDC2 heterogeneity and identified various cDC2 progenitors beyond the common DC progenitor (CDP), hinting at distinct cDC2 lineages. By generating Cd300ciCre-hCD2R26tdTomato reporter mice, we identified a bone marrow pro-cDC2 progenitor exclusively generating cDC2 in vitro and in vivo. Single-cell analyses and multiparametric flow cytometry demonstrated that pro-cDC2 encompass myeloid-derived pre-cDC2 and lymphoid-derived pDC-like precursors differentiating into a transcriptionally convergent cDC2 phenotype. Cd300c-traced cDC2 had distinct transcriptomic profiles, phenotypes, and tissue distributions compared to Ms4a3CreR26tdTomato lineage-traced DC3, a monocyte-DC progenitor-derived subset that bypasses CDP. Mice with reduced Cd300c-traced cDC2 showed impaired humoral responses to a blood-borne antigen. We conclude that progenitors of distinct lineages shape the diversity of mature cDC2 cells across tissues. Thus, ontogenesis may impact tissue immune responses.

2024-05-29 | GSE262477 | GEO

Progenitors of distinct lineages shape the diversity of mature type 2 conventional dendritic cells [scRNA-Seq]

2024-05-29 | GSE262474 | GEO

RNA-seq of dendritic cell subsets

Project description:Comparison of cDC1, cDC2, mcDC transcriptome Conventional dendritic cells (cDCs) are classically subdivided in two subsets, named cDC1 and cDC2. We demonstrated that mcDC are a new subset of cDCs. To understand their transcriptomic relatedness, we perform a RNA sequencing on cDC1, cDC2 and mcDCs sorted from mouse spleens. We demonstrate that cDC1, cDC2 and mcDCs all cluster independently in a PCA analysis and an unbiased hierarchical cluster analysis reveals unique gene profile for all three cDC subsets. As mcDC cluster slightly more towards cDC1 than cDC2, we next aimed to more closely examine the transcriptomic relatedness between mcDC and cDC2. We compared the DC subsets gene expression signatures based on a selected gene set known to define cDC2. Both the PCA and hierarchical cluster analysis show that mcDC exhibit a different signature to cDC2. Altogether, we demonstrate that mcDC are a distinct subsets of cDCs with a specific transcriptomic signature.

2020-04-30 | GSE147458 | GEO

Clonal lineage tracing reveals shared origin of conventional and plasmacytoid dendritic cells

Project description:Developmental origins of dendritic cells (DCs) including conventional DCs (cDCs, comprising cDC1 and cDC2 subsets) and plasmacytoid DCs (pDCs) remain unclear. We studied DC development in unmanipulated adult mice using inducible lineage tracing combined with clonal DNA "barcoding" and single-cell transcriptome and phenotype analysis (CITE-Seq). Inducible tracing of Cx3cr1+ hematopoietic progenitors in the bone marrow showed that they simultaneously produce all DC subsets including pDCs, cDC1s and cDC2s. Clonal tracing of hematopoietic stem cells (HSCs) and of Cx3cr1+ progenitors revealed clone sharing between cDC1s and pDCs, but not between the two cDC subsets or between pDCs and B cells. Accordingly, CITE-Seq analyses of differentiating HSCs and Cx3cr1+ progenitors identified progressive stages of pDC development including Cx3cr1+ Ly-6D+ propDCs that were distinct from lymphoid progenitors. These results reveal the shared origin of pDCs and cDCs, and suggest a revised scheme of DC development whereby pDCs share clonal relationship with cDC1s

2022-02-16 | GSE193733 | GEO

Transcriptional identity and function of human dendritic cells is dictated by origin not tissue microenvironment

Project description:It has been well established that murine myeloid and plasmacytoid dendritic cells (DCs) derive from a separate hematopoietic precursor before they migrate via the blood stream to peripheral tissues. Moreover, two classes of murine conventional DCs (cDC1 and cDC2 DCs) and one class of plasmacytoid DCs (pDCs) were shown to be transcriptionally and functionally distinct entities. In humans, these DC subtypes have also been identified based on the cell surface markers CD1c (cDC2), CD141 (cDC1), and CD303 (pDCs), albeit it still remains elusive whether DC functionality is mainly determined by ontogeny or the tissue microenvironment. Moreover, an in-depth analysis of their transcriptome in different human tissues has not been established. By phenotypic and transcriptional profiling of these three DC subtypes in different human tissues derived from a larger number of human individuals, we here demonstrate that DC subpopulations – in contrast to macrophages – are more strongly defined by ontogeny rather than their localization. We provide a compendium of novel markers distinguishing DCs in different human tissues. Furthermore, bioinformatical modeling revealed a network of DC subtype-specific transcriptional regulators (TRs). Particularly CD141+ DCs were underrepresented in previous data as determined by gene set enrichment analysis using ImmuneSigDB signatures. Collectively, the data provided in this study should serve the community as a rich resource guiding further studies into human DC biology during homeostasis and inflammation.

2016-12-24 | GSE77671 | GEO

A lncRNA identifies Irf8 enhancer element in negative feedback control of dendritic cell differentiation

Project description:Dendritic cells (DC) are professional antigen presenting cells that develop from multipotent progenitors (MPP) and DC committed common DC progenitors (CDP) and further differentiate into different subsets: classical DC type 1 and 2 (cDC1 and cDC2, respectively) and plasmacytoid DC (pDC). In this study MPP, CDP, cDC1, cDC2 and pDC were obtained in a two-step in vitro culture system according to Felker et al., J. Immunol. 185, 5326-5335, 2010. Briefly, mouse bone marrow cells were first amplified with a specific cytokine cocktail and then induced to differentiate into DC with Flt3 ligand. MPP, CDP, cDC1, cDC2 and pDC were obtained by FACS sorting as follows: MPP: Gr1- CD117hi CD135low/-; CDP: Gr1- CD117int CD135+ CD115+; cDC1: CD11c+ CD11blow/- XCR1+; cDC2: CD11c+ CD11b+ XCR1- and pDC: CD11c+ CD11b- B220+. FACS sorted cells were then subjected to Omni-ATAC-seq, nuclear-titrated (NuTi) Capture-C targeting Irf8 promoter, and RNA-seq analysis. ATAC-seq data of cDC1 and pDC are published (Li et al., Genome Biol. 20, 45, 2019; GSE118221). ATAC-seq data of MPP, CDP and cDC2, NuTi Capture-C and RNA-seq data of MPP, CDP, cDC1, cDC2 and pDC are published here. CD11c+ CD11b+ B220- cDC and CD11c+ CD11b- B220+ pDC were obtained by FACS sorting and subjected to ChIP-seq analysis of IRF8 and are published here.

2023-03-01 | GSE198651 | GEO

Epigenetic and transcriptional regulation of dendritic cell development and anti-tumor function by HDAC1 (CUT&RUN)

Project description:DC progenitors adapt their transcriptional program during development generating different subsets. How chromatin modifications modulate these processes is unclear. Here we investigate the impact of histone deacetylation on DCs by genetically deleting HDAC1 or HDAC2 in hematopoietic progenitors and CD11c-expressing cells. While HDAC2 isn’t critical for DC development, HDAC1 deletion impairs pro- and mature pDC generation and affects ESAM+cDC2 differentiation from tDC and pre-cDC2, whereas cDC1s are unchanged. HDAC1 knock-down in human hematopoietic cells also impairs cDC2 development highlighting its crucial role across species. Multi-omics analyses reveal that HDAC1 controls expression, chromatin accessibility and histone-acetylation of the transcription factors IRF4, IRF8 and SPIB required for efficient development of cDC2 subsets. Without HDAC1, DCs switch immunologically enhancing tumor surveillance through increased cDC1 maturation and IL-12 production driving Th1-mediated immunity and CD8+T-cell recruitment. Our study reveals the importance of histone-acetylation in DC development and anti-tumor immunity suggesting DC-targeted therapeutic strategies for immuno-oncology.

2024-05-30 | GSE266582 | GEO

Epigenetic and transcriptional regulation of dendritic cell development and anti-tumor function by HDAC1 (ATAC-Seq)

2024-05-30 | GSE266581 | GEO

Epigenetic and transcriptional regulation of dendritic cell development and anti-tumor function by HDAC1 (RNA-Seq)

2024-05-30 | GSE266583 | GEO

DC-SCRIPT (Zpf366) binding in cDC1 and cDC2 cells from wildtype and DC-SCRIPT knockout mice

Project description:The functional diversification of dendritic cells (DCs) is a key step in establishing protective immune responses. Despite the importance of this lineage diversity, its genetic basis is not fully understood. DC-SCRIPT (Zfp366) is a poorly known transcription factor expressed in conventional DCs (cDCs) and their committed bone marrow progenitors but not in plasmacytoid DCs (pDCs). We show that mice lacking DC-SCRIPT displayed substantially impaired development of IRF8-dependent conventional DC1 (cDC1), while cDC2 differentiated normally. The residual DC-SCRIPT-deficient cDC1s had impaired CD8+ T-cell cross-priming, which could be in part explained by the direct control of DC-SCRIPT on IL-12p40 production. Genome-wide mapping of DC-SCRIPT binding and gene expression analyses revealed a key role for DC-SCRIPT in maintaining cDC1 identity via the direct regulation of cDC1 signature genes, including Irf8. Our study reveals DC-SCRIPT to be a critical component of the gene regulatory program shaping the functional attributes of cDC1s.

2021-02-24 | GSE165138 | 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