Evidence map›Paper›PMID 26056000›Full record

ArticleGenome biology2015

Deep sequencing reveals cell-type-specific patterns of single-cell transcriptome variation.

Hannah Dueck, Mugdha Khaladkar, Tae Kyung Kim, Jennifer M Spaethling, Chantal Francis, Sangita Suresh, Stephen A Fisher, Patrick Seale, Sheryl G Beck, Tamas Bartfai and 3 more

Abstract read
In one paragraph

Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. Cre driver mouse lines for thalamocortical circuit mapping.The Journal of comparative neurology · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Hannah DueckDepartment of Genomics and Computational Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. hdueck@mail.upenn.edu.
Mugdha KhaladkarDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, 301A/B Lynch Laboratory, 433 S University Avenue, Philadelphia, PA, 19104, USA. mugdhak@pcbi.upenn.edu.
Tae Kyung KimDepartment of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. sean.taekyung@gmail.com.
Jennifer M SpaethlingDepartment of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. jspaethl@mail.med.upenn.edu.
Chantal FrancisDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, 301A/B Lynch Laboratory, 433 S University Avenue, Philadelphia, PA, 19104, USA. chantalfedde@gmail.com.
Sangita SureshDepartment of Pediatrics, Harvard Medical School, Boston, MA, USA. sangita.suresh@gmail.com.
Stephen A FisherDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, 301A/B Lynch Laboratory, 433 S University Avenue, Philadelphia, PA, 19104, USA. safisher@sas.upenn.edu.
Patrick SealeDepartment of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. sealep@mail.med.upenn.edu.
Sheryl G BeckDepartment of Anesthesiology, The Children's Hospital of Philadelphia Research Institute, Philadelphia, PA, USA. BECKS@email.chop.edu.
Tamas BartfaiThe Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA, USA. tbartfai@scripps.edu.
Bernhard KuhnDepartment of Pediatrics, Harvard Medical School, Boston, MA, USA. Bernhard.Kuhn2@CHP.edu.
James EberwineDepartment of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. eberwine@mail.med.upenn.edu.
Junhyong KimDepartment of Biology, School of Arts and Sciences, University of Pennsylvania, 301A/B Lynch Laboratory, 433 S University Avenue, Philadelphia, PA, 19104, USA. junhyong@sas.upenn.edu.

Funding

Role of Single Cell mRNA Variation in Systems Associated Electrically Excitable CU01MH098953 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI EBERWINE, JAMES H, KIM, JUNHYONG · 2012 to 2016
$11.4M
Cellular logic of phenotypeDP1OD004117 · OD · UNIVERSITY OF PENNSYLVANIA · PI EBERWINE, JAMES H · 2008 to 2011
$3.1M
Myofibril disassembly during neonatal heart muscle cell proliferationR01HL106302 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KUHN, BERNHARD · 2011 to 2015
$2.1M
Single-cell comparative genomics of the neuronR01MH088849 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI EBERWINE, JAMES H, KIM, JUNHYONG · 2009 to 2012
$1.2M
Periostin in Myocardial Injury and RegenerationK08HL085143 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI KUHN, BERNHARD · 2009 to 2013
$645k
NHLBI NIH HHS K08 HL085143NHLBI NIH HHS R01 HL106302NHLBI NIH HHS R01HL106302NIH HHS DP1 OD004117NIMH NIH HHS 5R01MH088849NIMH NIH HHS 5U01MH098953NIMH NIH HHS R01 MH088849NIMH NIH HHS U01 MH098953
6 · The paper itself

Abstract

backgroundDifferentiation of metazoan cells requires execution of different gene expression programs but recent single-cell transcriptome profiling has revealed considerable variation within cells of seeming identical phenotype. This brings into question the relationship between transcriptome states and cell phenotypes. Additionally, single-cell transcriptomics presents unique analysis challenges that need to be addressed to answer this question.

resultsWe present high quality deep read-depth single-cell RNA sequencing for 91 cells from five mouse tissues and 18 cells from two rat tissues, along with 30 control samples of bulk RNA diluted to single-cell levels. We find that transcriptomes differ globally across tissues with regard to the number of genes expressed, the average expression patterns, and within-cell-type variation patterns. We develop methods to filter genes for reliable quantification and to calibrate biological variation. All cell types include genes with high variability in expression, in a tissue-specific manner. We also find evidence that single-cell variability of neuronal genes in mice is correlated with that in rats consistent with the hypothesis that levels of variation may be conserved.

conclusionsSingle-cell RNA-sequencing data provide a unique view of transcriptome function; however, careful analysis is required in order to use single-cell RNA-sequencing measurements for this purpose. Technical variation must be considered in single-cell RNA-sequencing studies of expression variation. For a subset of genes, biological variability within each cell type appears to be regulated in order to perform dynamic functions, rather than solely molecular noise.

Indexed as

Genetic VariationTranscriptomeAnimalsCells, CulturedGene Expression ProfilingHigh-Throughput Nucleotide SequencingMiceMice, Inbred C57BLRatsRats, Sprague-DawleyRNA StabilitySequence Analysis, RNASingle-Cell Analysis

Identifiers

PMID26056000
PMCPMC4480509

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.