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Series GSE60781 Query DataSets for GSE60781
Status Public on Jun 01, 2015
Title Identification of subset-specific dendritic cell progenitors reveals early commitment in the bone marrow [RNA-Seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Dendritic cells (DCs) are antigen sensing and presenting cells that are essential for effective immunity. Existing as a multi-subset population, divided by distinct developmental and functional characteristics1,2, DC subsets play important and unique roles in responses to pathogens, vaccines and cancer therapies, as well as during immune-pathologies. Therefore therapeutic manipulation of the DC compartment is an attractive strategy. However, our incomplete knowledge of the inter-relationship between DC subsets and how they develop from progenitors in the bone marrow (BM) has so far limited the realization of their therapeutic potential. DCs arise from a cascade of progenitors that gradually differentiate in the BM; first, the macrophage DC progenitor (MDP), then common DC progenitor (CDP), and lastly the Pre-DC, which will leave the BM to seed peripheral tissues before differentiating into mature DCs3,4. While the basic outline of this process is known, how subset commitment and development is regulated at the molecular level remains poorly understood. Here we reveal that the Pre-DC population in mice is heterogeneous, containing uncommitted Ly6c+/-Siglec-H+ cells as well as Ly6c+Siglec-H- and Ly6c-Siglec-H- sub-populations that are developmentally fated to become Th2/17-inducing CD11b+ DCs and Th1-inducing CD8α+ DCs, respectively. Using single cell analysis by microfluidic RNA sequencing, we found that DC subset imprinting occurred at the mRNA level from the CDP stage, revealing that subset fate is defined in the BM and not in peripheral tissues. Single cell transcriptome analysis allowed identification of the molecular checkpoints between progenitor stages and revealed new regulators of DC-poiesis, shedding light on the role of cell cycle control and specific transcription factors in DC lineage development. These data advance our knowledge of the steady-state regulation of DC populations and open promising new avenues for investigation of the therapeutic potential of DC subset-specific targeting in vivo to improve vaccine-based and immunotherapeutic strategies.
 
Overall design Single cell mRNA sequencing was used to investigate the transcriptomic relationships within the Dendritic cell precursor compartment within the BM as well as between single Dendritic cell precursors
 
Contributor(s) Schlitzer A, Chen J, Sivakamasundari V, Robson P, Poidinger M, Ginhoux F
Citation(s) 26054720
Submission date Aug 26, 2014
Last update date Mar 19, 2019
Contact name jinmiao chen
E-mail chen_jinmiao@immunol.a-star.edu.sg
Organization name Singapore Immunology Network
Street address 8A Biomedical Grove, #04-06 Immunos
City Singapore
ZIP/Postal code 138648
Country Singapore
 
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (251)
GSM1488302 CDP_1
GSM1488303 CDP_2
GSM1488304 CDP_3
This SubSeries is part of SuperSeries:
GSE60783 Identification of subset-specific dendritic cell progenitors reveals early commitment in the bone marrow
Relations
SRA SRP045794
BioProject PRJNA259535

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE60781_RAW.tar 22.3 Mb (http)(custom) TAR (of TXT)
GSE60781_RPKM.txt.gz 8.9 Mb (ftp)(http) TXT
Raw data are available in SRA
Processed data provided as supplementary file
Processed data is available on Series record

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