Single-cell transcriptomics reveals bimodality in expression and splicing in immune cells.


Recent molecular studies have shown that, even when derived from a seemingly homogenous population, individual cells can exhibit substantial differences in gene expression, protein levels and phenotypic output, with important functional consequences. Existing studies of cellular heterogeneity, however, have typically measured only a few pre-selected RNAs or proteins simultaneously, because genomic profiling methods could not be applied to single cells until very recently. Here we use single-cell RNA sequencing to investigate heterogeneity in the response of mouse bone-marrow-derived dendritic cells (BMDCs) to lipopolysaccharide. We find extensive, and previously unobserved, bimodal variation in messenger RNA abundance and splicing patterns, which we validate by RNA-fluorescence in situ hybridization for select transcripts. In particular, hundreds of key immune genes are bimodally expressed across cells, surprisingly even for genes that are very highly expressed at the population average. Moreover, splicing patterns demonstrate previously unobserved levels of heterogeneity between cells. Some of the observed bimodality can be attributed to closely related, yet distinct, known maturity states of BMDCs, other portions reflect differences in the usage of key regulatory circuits. For example, we identify a module of 137 highly variable, yet co-regulated, antiviral response genes. Using cells from knockout mice, we show that variability in this module may be propagated through an interferon feedback circuit, involving the transcriptional regulators Stat2 and Irf7. Our study demonstrates the power and promise of single-cell genomics in uncovering functional diversity between cells and in deciphering cell states and circuits.

GSE41265 Samples



Cell Metadata and BAM Files

Dataset Metadata

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
SRR578548 SAMN01737621 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578549 SAMN01737621 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578550 SAMN01737621 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578551 SAMN01737622 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578552 SAMN01737622 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578553 SAMN01737622 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578554 SAMN01737623 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578555 SAMN01737623 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578556 SAMN01737623 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578557 SAMN01737624 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578558 SAMN01737624 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578559 SAMN01737624 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578560 SAMN01737625 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578561 SAMN01737625 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578562 SAMN01737625 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578563 SAMN01737626 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578564 SAMN01737626 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578565 SAMN01737626 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578566 SAMN01737627 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578567 SAMN01737627 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578568 SAMN01737627 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578569 SAMN01737628 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578570 SAMN01737628 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578571 SAMN01737628 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578572 SAMN01737629 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578573 SAMN01737629 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578574 SAMN01737629 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578575 SAMN01737630 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578576 SAMN01737630 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578577 SAMN01737630 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR578578 SAMN01737631 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578579 SAMN01737631 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578580 SAMN01737631 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578581 SAMN01737632 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578582 SAMN01737632 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578583 SAMN01737632 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578584 SAMN01737633 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578585 SAMN01737633 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578586 SAMN01737633 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578587 SAMN01737634 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578588 SAMN01737634 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578589 SAMN01737634 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578590 SAMN01737635 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578591 SAMN01737635 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578592 SAMN01737635 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] S
SRR578593 SAMN01737636 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578594 SAMN01737636 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578595 SAMN01737636 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578596 SAMN01737637 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578597 SAMN01737637 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578598 SAMN01737637 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] M.G1
SRR578599 SAMN01737638 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578600 SAMN01737638 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578601 SAMN01737638 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578602 SAMN01737639 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578603 SAMN01737639 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578604 SAMN01737639 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578605 SAMN01737640 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578606 SAMN01737640 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578607 SAMN01737640 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578608 SAMN01737641 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578609 SAMN01737641 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR578610 SAMN01737641 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G1.S
SRR799682 SAMN01994505 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR799683 SAMN01994505 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2
SRR799684 SAMN01994506 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2.M
SRR799685 SAMN01994506 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2.M
SRR799686 SAMN01994507 Mus musculus Bone marrow Adult Dendritic cell Illumina HiSeq 2000 SMARTer RNA-Seq Paired-End CL:0000451 [dendritic cell] G2

FASTQC Report

Bulk Download

FASTQC File ID Cell Accession Number FASTQC Report Link No. Sequence Tags
SRR578548_1 Preview 7065766
SRR578548_2 Preview 7065766
SRR578549_1 Preview 7081581
SRR578549_2 Preview 7081581
SRR578550_1 Preview 7178701
SRR578550_2 Preview 7178701
SRR578551_1 Preview 8762922
SRR578551_2 Preview 8762922
SRR578552_1 Preview 9362647
SRR578552_2 Preview 9362647
SRR578553_1 Preview 9308442
SRR578553_2 Preview 9308442
SRR578554_1 Preview 9619357
SRR578554_2 Preview 9619357
SRR578555_1 Preview 10828269
SRR578555_2 Preview 10828269
SRR578556_1 Preview 10694765
SRR578556_2 Preview 10694765
SRR578557_1 Preview 8035212
SRR578557_2 Preview 8035212
SRR578558_1 Preview 9144992
SRR578558_2 Preview 9144992
SRR578559_1 Preview 9051648
SRR578559_2 Preview 9051648
SRR578560_1 Preview 9166757
SRR578560_2 Preview 9166757
SRR578561_1 Preview 10452514
SRR578561_2 Preview 10452514
SRR578562_1 Preview 10357943
SRR578562_2 Preview 10357943
SRR578563_1 Preview 7813112
SRR578563_2 Preview 7813112
SRR578564_1 Preview 8174530
SRR578564_2 Preview 8174530
SRR578565_1 Preview 8160745
SRR578565_2 Preview 8160745
SRR578566_1 Preview 8119591
SRR578566_2 Preview 8119591
SRR578567_1 Preview 7920275
SRR578567_2 Preview 7920275
SRR578568_1 Preview 8038250
SRR578568_2 Preview 8038250
SRR578569_1 Preview 7946851
SRR578569_2 Preview 7946851
SRR578570_1 Preview 8574470
SRR578570_2 Preview 8574470
SRR578571_1 Preview 8510805
SRR578571_2 Preview 8510805
SRR578572_1 Preview 7252243
SRR578572_2 Preview 7252243
SRR578573_1 Preview 7515278
SRR578573_2 Preview 7515278
SRR578574_1 Preview 7490161
SRR578574_2 Preview 7490161
SRR578575_1 Preview 9421315
SRR578575_2 Preview 9421315
SRR578576_1 Preview 10041330
SRR578576_2 Preview 10041330
SRR578577_1 Preview 9973644
SRR578577_2 Preview 9973644
SRR578578_1 Preview 9672123
SRR578578_2 Preview 9672123
SRR578579_1 Preview 10722184
SRR578579_2 Preview 10722184
SRR578580_1 Preview 10735971
SRR578580_2 Preview 10735971
SRR578581_1 Preview 6814517
SRR578581_2 Preview 6814517
SRR578582_1 Preview 7195919
SRR578582_2 Preview 7195919
SRR578583_1 Preview 7151159
SRR578583_2 Preview 7151159
SRR578584_1 Preview 9024335
SRR578584_2 Preview 9024335
SRR578585_1 Preview 9848382
SRR578585_2 Preview 9848382
SRR578586_1 Preview 9740116
SRR578586_2 Preview 9740116
SRR578587_1 Preview 8224518
SRR578587_2 Preview 8224518
SRR578588_1 Preview 9064141
SRR578588_2 Preview 9064141
SRR578589_1 Preview 9062530
SRR578589_2 Preview 9062530
SRR578590_1 Preview 8168995
SRR578590_2 Preview 8168995
SRR578591_1 Preview 8821823
SRR578591_2 Preview 8821823
SRR578592_1 Preview 8748757
SRR578592_2 Preview 8748757
SRR578593_1 Preview 8525597
SRR578593_2 Preview 8525597
SRR578594_1 Preview 9183687
SRR578594_2 Preview 9183687
SRR578595_1 Preview 9093062
SRR578595_2 Preview 9093062
SRR578596_1 Preview 8266431
SRR578596_2 Preview 8266431
SRR578597_1 Preview 9093757
SRR578597_2 Preview 9093757
SRR578598_1 Preview 8983334
SRR578598_2 Preview 8983334
SRR578599_1 Preview 8477944
SRR578599_2 Preview 8477944
SRR578600_1 Preview 8378549
SRR578600_2 Preview 8378549
SRR578601_1 Preview 8433580
SRR578601_2 Preview 8433580
SRR578602_1 Preview 9339929
SRR578602_2 Preview 9339929
SRR578603_1 Preview 9419489
SRR578603_2 Preview 9419489
SRR578604_1 Preview 9488408
SRR578604_2 Preview 9488408
SRR578605_1 Preview 12193169
SRR578605_2 Preview 12193169
SRR578606_1 Preview 13598736
SRR578606_2 Preview 13598736
SRR578607_1 Preview 13511971
SRR578607_2 Preview 13511971
SRR578608_1 Preview 9932826
SRR578608_2 Preview 9932826
SRR578609_1 Preview 9897814
SRR578609_2 Preview 9897814
SRR578610_1 Preview 10000641
SRR578610_2 Preview 10000641
SRR799682_1 Preview 8000000
SRR799682_2 Preview 8000000
SRR799683_1 Preview 5848219
SRR799683_2 Preview 5848219
SRR799684_1 Preview 8000000
SRR799684_2 Preview 8000000
SRR799685_1 Preview 5550218
SRR799685_2 Preview 5550218
SRR799686_1 Preview 8000000
SRR799686_2 Preview 8000000

Organism : Mus musculus

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File Size : 143M

Mouse Cell Data

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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 Krona Plot Img Link Unmapped Reads Link Expression Correlation
Mus musculus