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

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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


FASTQC File ID Cell Accession Number FASTQC Report Link No. Sequence Tags
SRR578548_1 SRR578548 Preview 7065766
SRR578548_2 SRR578548 Preview 7065766
SRR578549_1 SRR578549 Preview 7081581
SRR578549_2 SRR578549 Preview 7081581
SRR578550_1 SRR578550 Preview 7178701
SRR578550_2 SRR578550 Preview 7178701
SRR578551_1 SRR578551 Preview 8762922
SRR578551_2 SRR578551 Preview 8762922
SRR578552_1 SRR578552 Preview 9362647
SRR578552_2 SRR578552 Preview 9362647
SRR578553_1 SRR578553 Preview 9308442
SRR578553_2 SRR578553 Preview 9308442
SRR578554_1 SRR578554 Preview 9619357
SRR578554_2 SRR578554 Preview 9619357
SRR578555_1 SRR578555 Preview 10828269
SRR578555_2 SRR578555 Preview 10828269
SRR578556_1 SRR578556 Preview 10694765
SRR578556_2 SRR578556 Preview 10694765
SRR578557_1 SRR578557 Preview 8035212
SRR578557_2 SRR578557 Preview 8035212
SRR578558_1 SRR578558 Preview 9144992
SRR578558_2 SRR578558 Preview 9144992
SRR578559_1 SRR578559 Preview 9051648
SRR578559_2 SRR578559 Preview 9051648
SRR578560_1 SRR578560 Preview 9166757
SRR578560_2 SRR578560 Preview 9166757
SRR578561_1 SRR578561 Preview 10452514
SRR578561_2 SRR578561 Preview 10452514
SRR578562_1 SRR578562 Preview 10357943
SRR578562_2 SRR578562 Preview 10357943
SRR578563_1 SRR578563 Preview 7813112
SRR578563_2 SRR578563 Preview 7813112
SRR578564_1 SRR578564 Preview 8174530
SRR578564_2 SRR578564 Preview 8174530
SRR578565_1 SRR578565 Preview 8160745
SRR578565_2 SRR578565 Preview 8160745
SRR578566_1 SRR578566 Preview 8119591
SRR578566_2 SRR578566 Preview 8119591
SRR578567_1 SRR578567 Preview 7920275
SRR578567_2 SRR578567 Preview 7920275
SRR578568_1 SRR578568 Preview 8038250
SRR578568_2 SRR578568 Preview 8038250
SRR578569_1 SRR578569 Preview 7946851
SRR578569_2 SRR578569 Preview 7946851
SRR578570_1 SRR578570 Preview 8574470
SRR578570_2 SRR578570 Preview 8574470
SRR578571_1 SRR578571 Preview 8510805
SRR578571_2 SRR578571 Preview 8510805
SRR578572_1 SRR578572 Preview 7252243
SRR578572_2 SRR578572 Preview 7252243
SRR578573_1 SRR578573 Preview 7515278
SRR578573_2 SRR578573 Preview 7515278
SRR578574_1 SRR578574 Preview 7490161
SRR578574_2 SRR578574 Preview 7490161
SRR578575_1 SRR578575 Preview 9421315
SRR578575_2 SRR578575 Preview 9421315
SRR578576_1 SRR578576 Preview 10041330
SRR578576_2 SRR578576 Preview 10041330
SRR578577_1 SRR578577 Preview 9973644
SRR578577_2 SRR578577 Preview 9973644
SRR578578_1 SRR578578 Preview 9672123
SRR578578_2 SRR578578 Preview 9672123
SRR578579_1 SRR578579 Preview 10722184
SRR578579_2 SRR578579 Preview 10722184
SRR578580_1 SRR578580 Preview 10735971
SRR578580_2 SRR578580 Preview 10735971
SRR578581_1 SRR578581 Preview 6814517
SRR578581_2 SRR578581 Preview 6814517
SRR578582_1 SRR578582 Preview 7195919
SRR578582_2 SRR578582 Preview 7195919
SRR578583_1 SRR578583 Preview 7151159
SRR578583_2 SRR578583 Preview 7151159
SRR578584_1 SRR578584 Preview 9024335
SRR578584_2 SRR578584 Preview 9024335
SRR578585_1 SRR578585 Preview 9848382
SRR578585_2 SRR578585 Preview 9848382
SRR578586_1 SRR578586 Preview 9740116
SRR578586_2 SRR578586 Preview 9740116
SRR578587_1 SRR578587 Preview 8224518
SRR578587_2 SRR578587 Preview 8224518
SRR578588_1 SRR578588 Preview 9064141
SRR578588_2 SRR578588 Preview 9064141
SRR578589_1 SRR578589 Preview 9062530
SRR578589_2 SRR578589 Preview 9062530
SRR578590_1 SRR578590 Preview 8168995
SRR578590_2 SRR578590 Preview 8168995
SRR578591_1 SRR578591 Preview 8821823
SRR578591_2 SRR578591 Preview 8821823
SRR578592_1 SRR578592 Preview 8748757
SRR578592_2 SRR578592 Preview 8748757
SRR578593_1 SRR578593 Preview 8525597
SRR578593_2 SRR578593 Preview 8525597
SRR578594_1 SRR578594 Preview 9183687
SRR578594_2 SRR578594 Preview 9183687
SRR578595_1 SRR578595 Preview 9093062
SRR578595_2 SRR578595 Preview 9093062
SRR578596_1 SRR578596 Preview 8266431
SRR578596_2 SRR578596 Preview 8266431
SRR578597_1 SRR578597 Preview 9093757
SRR578597_2 SRR578597 Preview 9093757
SRR578598_1 SRR578598 Preview 8983334
SRR578598_2 SRR578598 Preview 8983334
SRR578599_1 SRR578599 Preview 8477944
SRR578599_2 SRR578599 Preview 8477944
SRR578600_1 SRR578600 Preview 8378549
SRR578600_2 SRR578600 Preview 8378549
SRR578601_1 SRR578601 Preview 8433580
SRR578601_2 SRR578601 Preview 8433580
SRR578602_1 SRR578602 Preview 9339929
SRR578602_2 SRR578602 Preview 9339929
SRR578603_1 SRR578603 Preview 9419489
SRR578603_2 SRR578603 Preview 9419489
SRR578604_1 SRR578604 Preview 9488408
SRR578604_2 SRR578604 Preview 9488408
SRR578605_1 SRR578605 Preview 12193169
SRR578605_2 SRR578605 Preview 12193169
SRR578606_1 SRR578606 Preview 13598736
SRR578606_2 SRR578606 Preview 13598736
SRR578607_1 SRR578607 Preview 13511971
SRR578607_2 SRR578607 Preview 13511971
SRR578608_1 SRR578608 Preview 9932826
SRR578608_2 SRR578608 Preview 9932826
SRR578609_1 SRR578609 Preview 9897814
SRR578609_2 SRR578609 Preview 9897814
SRR578610_1 SRR578610 Preview 10000641
SRR578610_2 SRR578610 Preview 10000641
SRR799682_1 SRR799682 Preview 8000000
SRR799682_2 SRR799682 Preview 8000000
SRR799683_1 SRR799683 Preview 5848219
SRR799683_2 SRR799683 Preview 5848219
SRR799684_1 SRR799684 Preview 8000000
SRR799684_2 SRR799684 Preview 8000000
SRR799685_1 SRR799685 Preview 5550218
SRR799685_2 SRR799685 Preview 5550218
SRR799686_1 SRR799686 Preview 8000000
SRR799686_2 SRR799686 Preview 8000000

Organism : Mus musculus

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File Size : 143M

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