Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The clonal and molecular aetiology of Flt3L-mediated ‘emergency’ dendritic cell development

ABSTRACT: The clonal and molecular aetiology of Flt3L-mediated ‘emergency’ dendritic cell development

PROVIDER: PRJNA622704 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11470678_1.fastq.gz	Fastqsanger.gz
	SRR11470678_2.fastq.gz	Fastqsanger.gz
	SRR11470679_1.fastq.gz	Fastqsanger.gz
	SRR11470679_2.fastq.gz	Fastqsanger.gz
	SRR11470680_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 12

Similar Datasets

The clonal and molecular aetiology of Flt3L-mediated ‘emergency’ dendritic cell development

Project description:Flt3 ligand (Flt3L) promotes an increased generation of type 1 conventional dendritic cells (cDC1s), resulting in enhanced immunity against infections and cancer. Here, we employ cellular barcoding to understand how Flt3L regulates single haematopoietic stem and progenitor cell (HSPC) fate. Our results demonstrate that although Flt3L stimulation can recruit some additional cDC1-generating HSPCs, the major contributing factor to higher cDC1 numbers is through enhanced clonal expansion. This selective cDC1 expansion occurs primarily via multi-/oligo-potent clones, without compromising their clonal output to other lineages. We then develop Divi-Seq to simultaneously profile division history, surface phenotype and the transcriptional state of single HSPCs during the early phase of the response. We discover that Flt3L-responsive HSPCs maintain a proliferative ‘early progenitor’-like state, which leads to a selective emergence of CD11c+cKit+ transitional precursors with high cellular output to cDC1s. These findings inform the mechanistic action of Flt3L in natural immunity and immunotherapy.

2020-04-03 | GSE147977 | GEO

Clonal multi-omics reveals Bcor as a regulator of dendritic cell development and its action at a clonal level

Project description:Despite major developments in single cell multi-omics approaches, a single stem or progenitor cell can only be tested once. Here we develop ‘clonal multi-omics’, where recent daughters of a clone act as surrogates of the parental cell allowing multiple tests of its molecular profile and/or cellular fate under different conditions. We first present SIS-seq – a novel clonal method whereby siblings are examined in parallel for gene expression by RNA-seq, or for fate after culture. We use this method to identify, then validate using CRISPR, the genes expressed in single haematopoietic progenitors that control the development of the different dendritic cell (DC) subtypes. In this way, Bcor is identified as a suppressor of plasmacytoid DC (pDC) and conventional DC subtype 2 (cDC2) numbers during Flt3 ligand-mediated ‘emergency’ DC development. Using a complementary method SIS-skew – where WT and BcorKO siblings of the same clone are examined in parallel for fate – we discover that Bcor restricts clonal expansion, especially for generation of cDC2s, and suppresses clonal fate potential, especially for pDCs. SIS-seq and SIS-skew therefore represent novel and broadly applicable clonal multi-omics approaches that could reveal the molecular and cellular mechanisms governing stem, immune, reprogrammed and cancer cell function at a single cell level, including after genetic or extrinsic factor perturbation.

2020-07-01 | GSE153675 | GEO

Expression data from Flt3L-derived bone marrow dendritic cells from WT or Clec9agfp/gfp mice treated or not with dead cells

Project description:DNGR-1 (CLEC9A) is expressed in CD8-like dendritic cells (DCs) and detects a ligand exposed on necrotic cells. We have characterized the transcripts that are induced in cultures of Flt3L-derived bone-marrow-derived WT or DNGR1-deficient DCs upon incubation with dead cells. Microarray analysis of the transcriptome of DNGR-1-deficient and WT DCs cultured with dead cells failed to reveal any DNGR-1-dependence in the transcriptional response to dead cells. Flt3L-BMDC from WT or DNGR-1-deficient (Clec9a gfp/gfp) mice were left untreated or were cultured for 5 hours with UV-treated dead cells at a 1:2 ratio. CD24hi CD11blow B220- CD8Î±+-like DC were purified by cell sorting and RNA was extracted. There were 3 replicates for each of the four experimental conditions.

2012-04-30 | E-GEOD-36435 | biostudies-arrayexpress

Gene expression dynamics of Flt3L induced ex vivo BMDC differentiation

Project description:To understand the gene expression dynamics during Flt3L induced Bone-marrow derived dendritic cell (BMDC) differentatiion we performed RNA-seq. Three distinct stages were chosen and included the initial bone marrow cells, the Common Myeloid Progenitor (CMP), and fully differentiated BMDC.

2023-11-06 | GSE107026 | GEO

DNA methylation dynamics of Flt3L induced ex vivo BMDC differentiation

Project description:To understand the DNA methylation dynamics during Flt3L induced Bone-marrow derived dendritic cell (BMDC) differentatiion we performed reduced representation bisulfite sequencing (RRBS). Three distinct stages were chosen and included the initial bone marrow cells, the Common Myeloid Progenitor (CMP), and fully differentiated BMDC.

2023-11-06 | GSE107027 | GEO

Flt3L therapy induces a Treg‐promoting cDC1 state in triple‐negative breast cancer

Project description:Conventional dendritic cells (cDCs) are at the forefront of activating the immune system to mount an anti‐tumor immune response. Flt3L is a cytokine required for DC development that can increase DC abundance in the tumor when administered therapeutically. However, the impact of Flt3L on the phenotype of distinct cDC subsets in the tumor microenvironment is still largely undetermined. Here, using multi‐omic single‐cell analysis, we show that Flt3L therapy increases all cDC subsets in orthotopic E0771 triple‐negative breast cancer, but this did not result in a reduction of tumor growth. Interestingly, a CD81+migcDC1 population, likely developing from cDC1, was induced upon Flt3L treatment. This subset is characterized by the expression of both canonical cDC1 markers as well as migratory cDC activation and regulatory markers and displayed a higher Treg‐inducing potential compared to other migcDCs. To shift the cDC phenotype towards a T‐cell stimulatory phenotype, CD40 agonist therapy was administered in combination with Flt3L. However, while αCD40 reduced tumor growth, Flt3L failed to improve the therapeutic response to αCD40 therapy. Interestingly, Flt3L+αCD40 combination therapy increased the abundance of Treg promoting CD81+migcDC1. Nonetheless, while Treg‐depletion and αCD40 therapy were synergistic, the addition of Flt3L to this combination did not result in any added benefit. Overall, these results indicate that merely increasing cDCs in the tumor by Flt3L treatment cannot improve anti‐tumor responses and therefore might not be beneficial for the treatment of triple‐negative breast cancer, though could still be of use to increase cDC numbers for autologous DC‐therapy.

2023-07-26 | GSE225539 | GEO

Expression data from Flt3L-derived bone marrow dendritic cells from WT or Clec9agfp/gfp mice treated or not with dead cells

2012-05-01 | GSE36435 | GEO

Gene expression profile of MHCII+ cell subsets from bone marrow culture with FLT3L or GM-CSF

Project description:BM culture comprises of various cell types including dendritic cells and macrophage-like cells. To understand the biology of BM-derived DCs, CD11c+MHCII+ cell subsets from BM cultures with FLT3L or GM-CSF were analyzed and are shown to have distinct transcriptional profiles.

2023-03-05 | GSE225321 | GEO

Cell-autonomous FLT3L shedding via ADAM10 mediates conventional dendritic cell development in mouse spleen

Project description:Cell-autonomous FLT3L shedding via ADAM10 mediates conventional dendritic cell development in mouse spleen

| PRJNA543088 | ENA

In Fanconi Anemia, impaired accumulation of bone marrow neutrophils during emergency granulopoiesis induces hematopoietic stem cell stress

Project description:Fanconi Anemia (FA) is an inherited disorder of DNA-repair caused by mutation in one of 20+ interrelated genes that repair intra-strand DNA crosslinks and rescue collapsed or stalled replication forks. The most common hematologic abnormality in FA is anemia, but progression to bone marrow failure (BMF), clonal hematopoiesis, or acute myeloid leukemia (AML) may also occur. In prior studies, we found that Fanconi DNA-repair is required for successful emergency granulopoiesis; the process for rapid neutrophil production during the innate immune response. Specifically, Fancc-/- mice did not develop neutrophilia in response to emergency granulopoiesis stimuli, but instead exhibited apoptosis of bone marrow hematopoietic stem cells (HSCs) and differentiating neutrophils. Repeated emergency granulopoiesis challenges induced BMF in most Fancc-/- mice, with AML in survivors. In contrast, we found equivalent emergency granulopoiesis-induced neutrophilia in Fancc-/-Tp53+/- mice and wild type (WT) mice, without BMF in either. Since bone marrow neutrophil accumulation triggers termination of emergency granulopoiesis, we hypothesize neutrophilia protects Fancc-/-Tp53+/- bone marrow from the stress of sustained inflammatory physiology, as experienced by Fancc-/- mice.

2024-08-28 | GSE267161 | 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