Evidence map›Paper›PMID 35672358›Full record

ArticleNature communications2022

Single-cell RNA-sequencing of peripheral blood mononuclear cells reveals widespread, context-specific gene expression regulation upon pathogenic exposure.

Roy Oelen, Dylan H de Vries, Harm Brugge, M Grace Gordon, Martijn Vochteloo, single-cell eQTLGen consortium, BIOS Consortium, Chun J Ye, Harm-Jan Westra, Lude Franke and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
93citing papers in PubMed, 4 pooled it
11.4field-weighted citation impact, top 1% of its field
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

93 citing papers in PubMed, 4 syntheses or guidelines pooled it, 115 citations in OpenAlex.

  1. Pooled it
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  4. Integration ofFrontiers in immunology · 2023
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33 more citing papers are in PubMed but not listed here.

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

11 authors at 2 institutions in 2 countries.

Roy Oelen *Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-5026-6531
Dylan H de Vries *Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-0953-0257
Harm Brugge *Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
M Grace GordonBiological and Medical Informatics Graduate Program, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4321-9187
Martijn VochtelooDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-6385-0550
single-cell eQTLGen consortium
BIOS Consortium
Chun J YeInstitute for Human Genetics, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6560-3783
Harm-Jan WestraDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Lude FrankeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. l.h.franke@umcg.nl.
Monique G P van der WijstDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. m.g.p.van.der.wijst@umcg.nl.ORCID http://orcid.org/0000-0003-1520-3970
University Medical Center Groningen · NLUniversity of California, San Francisco · US

Funding

RESOURCE-BASED CENTER FOR THE ADVANCEMENT OF PRECISION MEDICINE IN RHEUMATOLOGYP30AR070155 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mary C Nakamura · 2016 to 2026
$8.2M
Genetic regulation and immunological function of ERAP2 haplotypesR01AI136972 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2018 to 2022
$3.5M
Fine mapping rheumatic disease variants using functional genomic sequencingR01AR071522 · NIAMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2017 to 2020
$1.5M
Fine mapping rheumatic disease variants using functional genomic sequencingU01HG012192 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YE, CHUN JIMMIE · 2021 to 2021
$526k
Utilizing single-cell Massively Parallel Reporter Assays to dissect gene by environment interactionsF31HG011007 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GORDON, MARY GRACE · 2020 to 2022
$117k
NHGRI NIH HHS F31 HG011007NHGRI NIH HHS U01 HG012192NIAID NIH HHS R01 AI136972NIAMS NIH HHS P30 AR070155NIAMS NIH HHS R01 AR071522
6 · The paper itself

Abstract

The host's gene expression and gene regulatory response to pathogen exposure can be influenced by a combination of the host's genetic background, the type of and exposure time to pathogens. Here we provide a detailed dissection of this using single-cell RNA-sequencing of 1.3M peripheral blood mononuclear cells from 120 individuals, longitudinally exposed to three different pathogens. These analyses indicate that cell-type-specificity is a more prominent factor than pathogen-specificity regarding contexts that affect how genetics influences gene expression (i.e., eQTL) and co-expression (i.e., co-expression QTL). In monocytes, the strongest responder to pathogen stimulations, 71.4% of the genetic variants whose effect on gene expression is influenced by pathogen exposure (i.e., response QTL) also affect the co-expression between genes. This indicates widespread, context-specific changes in gene expression level and its regulation that are driven by genetics. Pathway analysis on the CLEC12A gene that exemplifies cell-type-, exposure-time- and genetic-background-dependent co-expression interactions, shows enrichment of the interferon (IFN) pathway specifically at 3-h post-exposure in monocytes. Similar genetic background-dependent association between IFN activity and CLEC12A co-expression patterns is confirmed in systemic lupus erythematosus by in silico analysis, which implies that CLEC12A might be an IFN-regulated gene. Altogether, this study highlights the importance of context for gaining a better understanding of the mechanisms of gene regulation in health and disease.

Indexed as

Leukocytes, MononuclearLupus Erythematosus, SystemicGene Expression RegulationHumansLectins, C-TypeReceptors, MitogenRNASignal TransductionCLEC12A protein, humanLectins, C-TypeReceptors, MitogenRNA

Identifiers

PMID35672358
PMCPMC9174272
OpenAlexW4282024710

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.