Evidence map›Paper›PMID 39476533›Full record

ArticleEBioMedicine2024

Single-cell RNA transcriptomics in mice reveals embryonic origin of fibrosis due to maternal obesity.

Md Nazmul Hossain, Yao Gao, Xinrui Li, Liang Zhao, Xiangdong Liu, Jeanene Marie de Avila, Mei-Jun Zhu, Min Du

Erratum issuedAbstract read
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In one paragraph

Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–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

7 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Md Nazmul HossainNutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA.
Yao GaoNutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA.
Xinrui LiNutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA.
Liang ZhaoNutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA; College of Animal Science and Technology, Nanjing Agricultural University, China.
Xiangdong LiuNutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA; Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA.
Jeanene Marie de AvilaNutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA.
Mei-Jun ZhuSchool of Food Science, Washington State University, Pullman, WA, 99164, USA.
Min DuNutrigenomics and Growth Biology Laboratory, Department of Animal Sciences, Washington State University, Pullman, WA, 99164, USA. Electronic address: min.du@wsu.edu.

Funding

Maternal obesity, AMPK and fetal brown adipogenesisR01HD067449 · NICHD · WASHINGTON STATE UNIVERSITY · PI MIN DU · 2010 to 2026
$4.6M
NICHD NIH HHS R01 HD067449
6 · The paper itself

Abstract

backgroundOver 40% of pregnant women in the USA are obese which negatively affects fetal development and offspring health. Maternal obesity (MO) leads to fibrotic infiltration in multiple tissues and organs of offspring during their adulthood although the origin and mechanisms are unclear.

methodsC57BL/6J female mice were fed a control and high-fat diet to mimic MO condition. Embryonic somatic tissues were obtained at E9.5, E11.5, and E13.5 (equivalent to 6 weeks of human pregnancy) from control (CON) and MO mice for single-cell RNA-sequencing (scRNA-seq). To explore the role of AMP-activated protein kinase (AMPK), AMPK was activated by metformin and A769662, and knocked out in embryonic mesenchymal cells (EMC) using AMPKα1 floxed mice.

findingsUsing unsupervised clustering, we identified three major cell populations with fibrogenic capacity. Compared to CON, the population of fibrogenic cells increased dramatically (by ∼125%) due to MO, supporting an embryonic origin of fibrosis in the offspring. MO induced inflammatory response and elevated expression of transforming growth factor β (TGFβ) signalling and fibrogenic genes in embryos. MO inhibited AMPK and its activation by metformin and A769662 inhibited TGFβ signalling and fibrogenesis.

interpretationMO profoundly enhances embryonic fibrogenesis, explaining the origin of fibrosis in the offspring of mothers living with obesity. Our data underscore the importance of early intervention, before 5-6 weeks of pregnancy, in improving embryonic development, and AMPK is an amiable target for suppressing excessive fibrogenesis in MO embryos to assist increasing populations of obese mothers having healthy children.

fundingThis work was funded by National Institutes of Health Grant R01HD067449.

Indexed as

AMP-Activated Protein KinasesFibrosisPregnancy in ObesitySingle-Cell AnalysisTranscriptomeAnimalsDiet, High-FatDisease Models, AnimalFemaleGene Expression ProfilingHumansMetforminMiceMice, Inbred C57BLPregnancySignal TransductionAMP-Activated Protein KinasesMetforminTransforming Growth Factor betaAMPKEmbryoFibrogenesisMaternal obesityPRRX1scRNA-seqTGFβ

Identifiers

PMID39476533
PMCPMC11565040

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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.