SCPortalen


Single-cell analysis of CD4+ T-cell differentiation reveals three major cell states and progressive acceleration of proliferation.


Differentiation of lymphocytes is frequently accompanied by cell cycle changes, interplay that is of central importance for immunity but is still incompletely understood. Here, we interrogate and quantitatively model how proliferation is linked to differentiation in CD4+ T cells. We perform ex vivo single-cell RNA-sequencing of CD4+ T cells during a mouse model of infection that elicits a type 2 immune response and infer that the differentiated, cytokine-producing cells cycle faster than early activated precursor cells. To dissect this phenomenon quantitatively, we determine expression profiles across consecutive generations of differentiated and undifferentiated cells during Th2 polarization in vitro. We predict three discrete cell states, which we verify by single-cell quantitative PCR. Based on these three states, we extract rates of death, division and differentiation with a branching state Markov model to describe the cell population dynamics. From this multi-scale modelling, we infer a significant acceleration in proliferation from the intermediate activated cell state to the mature cytokine-secreting effector state. We confirm this acceleration both by live imaging of single Th2 cells and in an ex vivo Th1 malaria model by single-cell RNA-sequencing. The link between cytokine secretion and proliferation rate holds both in Th1 and Th2 cells in vivo and in vitro, indicating that this is likely a general phenomenon in adaptive immunity.

E-MTAB-3543 Samples



Cell Metadata and BAM Files

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BAM Files Run Accession Number Sample Accession Number Organism Organ/Tissue Dev. Stage Cell Type Sequencer Protocol Assay Type Library Layout Ontology Term Cell Cycle Phase
ERR873424 ERS717104 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] S
ERR873425 ERS717109 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] G2.M
ERR873426 ERS717119 Mus musculus Mediastinal Lymph Nodes Adult Naive T cells activated Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000898 [naive T cell] G2
ERR873427 ERS717103 Mus musculus Mediastinal Lymph Nodes Adult Naive T cells activated Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000898 [naive T cell] S
ERR873428 ERS717112 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] M.G1
ERR873429 ERS717111 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] M.G1
ERR873430 ERS717108 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] G1.S
ERR873431 ERS717102 Mus musculus Mediastinal Lymph Nodes Adult Naive T cells activated Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000898 [naive T cell] G2
ERR873432 ERS717105 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] S
ERR873433 ERS717107 Mus musculus Mediastinal Lymph Nodes Adult Naive T cells activated Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000898 [naive T cell] G2
ERR873434 ERS717114 Mus musculus Mediastinal Lymph Nodes Adult Naive T cells activated Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000898 [naive T cell] M.G1
ERR873435 ERS717115 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] M.G1
ERR873436 ERS717110 Mus musculus Mediastinal Lymph Nodes Adult Naive T cells activated Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000898 [naive T cell] G2
ERR873437 ERS717117 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] S
ERR873438 ERS717120 Mus musculus Mediastinal Lymph Nodes Adult Naive T cells activated Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000898 [naive T cell] G2
ERR873439 ERS717101 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] S
ERR873440 ERS717106 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] S
ERR873441 ERS717116 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] G2.M
ERR873442 ERS717118 Mus musculus Mediastinal Lymph Nodes Adult Naive T cells activated Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000898 [naive T cell] G2
ERR873443 ERS717113 Mus musculus Mediastinal Lymph Nodes Adult T helper cells subtype 2 Illumina HiSeq 2000 SMARTer RNA-Seq Single-End CL:0000546 [T-helper 2 cell ] M.G1

FASTQC Report



FASTQC File ID Cell Accession Number FASTQC Report Link No. Sequence Tags
ERR873424 ERR873424 Preview 11589494
ERR873425 ERR873425 Preview 14132273
ERR873426 ERR873426 Preview 75815085
ERR873427 ERR873427 Preview 52327404
ERR873428 ERR873428 Preview 16329069
ERR873429 ERR873429 Preview 15190666
ERR873430 ERR873430 Preview 16207558
ERR873431 ERR873431 Preview 80379572
ERR873432 ERR873432 Preview 16216971
ERR873433 ERR873433 Preview 79328104
ERR873434 ERR873434 Preview 65905457
ERR873435 ERR873435 Preview 13883633
ERR873436 ERR873436 Preview 72610535
ERR873437 ERR873437 Preview 13904942
ERR873438 ERR873438 Preview 71285493
ERR873439 ERR873439 Preview 14827849
ERR873440 ERR873440 Preview 14343217
ERR873441 ERR873441 Preview 13328110
ERR873442 ERR873442 Preview 80445956
ERR873443 ERR873443 Preview 14167351

Organism : Mus musculus

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File Size : 46M

Mouse Cell Data

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tSNE image.
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PCA image.
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Gene Body Coverage image.

Data Resources


Organism Run Metadata Link Data Repository Link Pubmed Record Link Author Provided Files DAVID Annotation Chart Link DAVID Annotation Table Link Gene Body Coverage Matrix Link PCA Matrix Link Krona Plot Img Link Unmapped Reads Link Expression Correlation
Mus musculus