Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Absence of Batf3 reveals a new dimension of phenotypic cell state plasticity within conventional dendritic cells

ABSTRACT: Conventional dendritic cells (cDCs) are traditionally subdivided into cDC1 and cDC2 lineages. Batf3 is a cDC1-required transcription factor, and we observed that Batf3-/- mice harbor a population of cDC1-like cells co-expressing cDC2-associated surface molecules. Using single cell RNA sequencing with integrated cell surface protein expression (CITE-seq), we found that Batf3-/- mitotic immature cDC1-like cells showed reduced expression of cDC1 features and increased levels of cDC2 features. In wildtype, we also observed a proportion of mature cDC1 cells expressing surface features characteristic to cDC2, and found that overall cDC cell state heterogeneity was mainly driven by developmental stage, proliferation and maturity. We detected population diversity within Sirpa+ cDC2 cells, including a Cd33+ cell state expressing high levels of Sox4 and lineage-mixed features characteristic to cDC1, cDC2, pDCs and monocytes. In conclusion, these data suggest that multiple cDC cell states can co-express lineage-overlapping features, revealing a level of previously unappreciated cDC plasticity.

ORGANISM(S): Mus musculus

PROVIDER: GSE149544 | GEO | 2021/02/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Irf8 deficiency induces functional, transcriptional and epigenetic reprogramming of cDC1 into the cDC2 lineage

Project description:Conventional dendritic cells (cDC) consist of two functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in mature cDC1 remains unclear. Here we used XCR1-cre to delete Irf8 in committed cDC1 and demonstrate that Irf8 is required for maintaining the identify of cDC1 but not their survival. In the absence of Irf8, committed cDC1 (“ex-cDC1”) acquired the transcriptional, functional and chromatin accessibility properties of cDC2. This conversion was independent on Irf4 and was associated with decreased accessibility in putative IRF8, Batf3 and composite AP-1-IRF (AICE) binding elements, together with increased accessibility of cDC2 associated transcription factor binding elements. Thus, IRF8 expression by committed cDC1 is required for preventing their conversion into cDC2.

2022-06-21 | GSE168477 | GEO

Transcriptional analysis of cDC subsets in Irf8+32 -/- and Zeb2 -165(d1+2+3) mice

Project description:To determine if the residual cDC subsets in the Δ1+2+3 and Δ32 mice reflected their normal counterparts, we performed bulk RNA-sequencing analysis of cDC1 and cDC2 from WT, Δ1+2+3 and Δ32 mice. cDC1 from WT and Δ1+2+3 clustered together in principal component analysis (PCA) plot, whereas cDC2 from WT and Δ32 mice cluster together. Further, cDC1 and cDC2 from WT mice show a large number of differentially expressed genes (DEGs), as expected. However, there were few DEGs in cDC1 between WT and Δ1+2+3 mice, or in cDC2 between WT and Δ32 mice, indicating no substantive transcriptional differences between corresponding cDC subsets in WT, Δ32 and Δ1+2+3 mice.

2024-05-29 | GSE268380 | GEO

Cell intrinsic Wnt4 influences cDC fate determination to suppress Type 2 immunity

Project description:We demonstrate that Wnt4, a beta-catenin independent Wnt ligand, is produced by both hematopoietic and non-hematopoietic cells and is both necessary and sufficient for pre-cDC1/cDC1 maintenance. Whereas BM cDC precursors undergo phosphoJNK/c-Jun activation upon Wnt4 treatment, loss of cDC Wnt4 in CD11cCreWnt4flox/flox mice impaired differentiation of CD24+, Clec9A+, CD103+ cDC1 compared to CD11cCre controls. Conversely, sc-RNAseq analysis of BM revealed a 2-fold increase in cDC2 gene signature genes and flow cytometry demonstrated increased numbers of SIRP-α + cDC2 amid lack of Wnt4. Increased cDC2 numbers due to CD11c-restricted Wnt4 deficiency increased interleukin 5 production, group 2 innate lymphoid cell (ILC2) expansion, and host resistance to the hookworm parasite Nippostrongylus brasiliensis. Collectively, these data uncover a novel and unexpected role for Wnt4 in cDC subset differentiation and Type 2 immunity.

2019-08-01 | GSE131569 | GEO

Retinoic acid directs the development and transcriptional programming of intestinal dendritic cells

Project description:This file contains gene microarray data from bone marrow pre-ul DC, in vitro derived CD103+CD11b+ and CD103+CD11b- cDC with or without retinoic acid. We analyze transcript expression data from bone marrow pre-uDC, Splenic and SI cDC1 and cDC2 (GSE15907 - 18 samples), in vitro derived CD103+CD11b+ and CD103+CD11b- cDC from C57Bl/6 mice. The complete dataset is linked below as a supplementary file.

2015-08-01 | E-GEOD-68399 | biostudies-arrayexpress

ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

Project description:The spleen contains phenotypically and functionally distinct cDC1 and cDC2 subpopulations, which each can be divided into several smaller and less-well characterized subsets. Despite advances in understanding the complexity of DC ontogeny and function by transcriptional programming, the significance of post-translational modifications in controlling tissue-specific cDC (subset) immunobiology remains elusive. Here, we identified the cell surface-expressed A-disintegrin-and-metalloproteinase 10 (ADAM10) as an essential regulator of cDC1 and cDC2 homeostasis in the splenic marginal zone (MZ). Mice with a CD11c-specific deletion of ADAM10 (ADAM10ΔCD11c) exhibited a complete loss of splenic ESAMhi cDC2A, because ADAM10 controlled their commitment, differentiation, survival, and EBI2-mediated localization within the MZ. Moreover, we discovered that ADAM10 is a molecular switch regulating cDC2 subset heterogeneity in the spleen, as this unbalanced cDC2A homeostasis in the absence of ADAM10 was compensated for by the emergence of a novel Clec12a+ cDC2B subset, closely resembling cDC2 generally found in peripheral lymph nodes. Moreover, in ADAM10ΔCD11c mice terminal differentiation of cDC1 was abrogated, resulting in reduced numbers of Langerin+ cDC1.

2021-09-06 | GSE154767 | GEO

ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

2023-06-27 | GSE154309 | 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

Single Cell RNA-Seq Analysis Reveals Fate Decision of Human Pre-cDC Determined by Transcription Factor Competition

Project description:Classic dendritic cells (cDCs) play a central role in the immune system and consist of two major subsets: CD141+ cDC (cDC1) and CD1c+ cDC (cDC2). The pre-cDCs is the immediate precursors to both cDC subsets. Previous studies showed that there were two pre-committed pre-cDC subpopulations. However, the key molecular drivers of pre-commitment in human pre-cDCs were not investigated. To address this question, we performed both single cell and bulk RNA sequencing (RNA-seq) of two cDC subsets and pre-cDCs. We inferred a list of sixteen candidate master regulator transcriptional factors (TFs) that can indeed separate pre-cDCs into two sub-populations, with one close to cDC1 and the other close to cDC2. More importantly, these two pre-cDC sub-populations are correlated with ratio of IRF8 to IRF4 expression level more than their individual expression level. Our results suggest the concept that the ratio of antagonistic TFs and their competition determine cDC subset differentiation fate.

2019-07-16 | GSE89322 | GEO

Identification of Transcription Factor Binding Sites using ATAC-seq

Project description:Dendritic cells (DC) are professional antigen presenting cells that comprise different subsets: classical DC type 1 and 2 (cDC1 and cDC2, respectively) and plasmacytoid DC (pDC). In this study cDC1 or 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. cDC1 are CD11c+ CD11b+ XCR1+ and pDC are CD11c+ CD11b- B220+ and thus cDC1 and pDC were obtained by FACS sorting and subjected to Omin-ATAC-seq analysis. As an example of practical application of HINT-ATAC, we performed Omin-ATAC-seq experiments of cDC and pDC cell populations and used HINT-ATAC to detect footprints within ATAC-seq peaks of each of these two cells. Next, we estimated changes in binding activity for all factors with a motif in JASPAR. Cell-specific TF activity is measured by the depth of footprints and number of reads flanking regions. Two known cDC factors, BATF3 and HES1, are detected. In summary, we demonstrated that HINT-ATAC is capable of identifying relevant factors for dendritic cell specification.

2019-01-15 | GSE118221 | GEO

cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity

Project description:CD4 T cells are thought to help promote anti-tumour responses by ‘licensing’ antigen presenting cells (APCs) that activate CD8 T cells. Conventional type 1 dendritic cells (cDC1s) are responsible for cross-presentation of tumour-derived antigens to CD8 T cells. Prevailing models presume that the cDC1 is licensed by CD4 T cells that are themselves activated by a distinct cDC subset, the cDC2. The recent finding that neoantigens presented by major histocompatibility complex (MHC) class II molecules can promote rejection of tumours that lack MHC class II (MHC-II) surface expression is consistent with an indirect action of CD4 T cells, such as cDC1 licensing. However, no study has directly identified the APC that primes the CD4 T cells responsible for licensing or clearly identified the target of CD4 licensing in vivo. Here, we generated cDC1-specific Cre expressing mouse strain to inactivate or induce expression of MHC-I, MHC-II, or CD40 specifically within the cDC1 lineage. Using a tumour model that relies on CD8 T cells and CD4 T cells for rejection, we discovered that early priming of CD4 T cells against tumour-derived antigens, in contrast to soluble antigens, relied overwhelmingly on the cDC1 and not the cDC2. cDC1 do not simply transport antigen to lymph nodes for processing by cDC2, since lack of MHC-II expression on cDC1 prevented CD4 T cell priming. We also found that CD40 signaling not only affects licensing of cDC1 for CD8 T cell priming, but is also critical for the activation of CD4 T cells. Thus, in the setting of tumour-derived antigens, cDC1 can function as an autonomous platform, capable of priming both CD4 and CD8 T cells and orchestrating their cross-talk required for optimal anti-tumour immunity.

2020-06-11 | GSE152196 | 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