Evidence map›Paper›PMID 35021856›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2022

Single-Cell Transcriptome Analysis Reveals Embryonic Endothelial Heterogeneity at Spatiotemporal Level and Multifunctions of MicroRNA-126 in Mice.

Fang-Hao Guo, Ya-Na Guan, Jun-Jun Guo, Lu-Jun Zhang, Jing-Jing Qiu, Yong Ji, Alex F Chen, Qing Jing

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

14 citing papers in PubMed, 38 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 1 institution in 2 countries.

Fang-Hao Guo *CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Innovation Center for Intervention of Chronic Disease and Promotion of Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, China (F.-H.G., Y.-N.G., J.-J.G., J.J.Q., Q.J.).
Ya-Na Guan *CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Innovation Center for Intervention of Chronic Disease and Promotion of Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, China (F.-H.G., Y.-N.G., J.-J.G., J.J.Q., Q.J.).
Jun-Jun GuoCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Innovation Center for Intervention of Chronic Disease and Promotion of Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, China (F.-H.G., Y.-N.G., J.-J.G., J.J.Q., Q.J.).
Lu-Jun ZhangDepartment of Cardiology, Changhai Hospital, Shanghai, China (L.-J.Z.).
Jing-Jing QiuCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Innovation Center for Intervention of Chronic Disease and Promotion of Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, China (F.-H.G., Y.-N.G., J.-J.G., J.J.Q., Q.J.).
Yong JiKey Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Key Laboratory of Cardiovascular and Cerebrovascular Medicine, Nanjing Medical University, Jiangsu, China (Y.J.).ORCID 0000-0003-2650-5747
Alex F ChenInstitute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, China (A.F.C.).ORCID 0000-0002-9792-0916
Qing JingCAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Innovation Center for Intervention of Chronic Disease and Promotion of Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, China (F.-H.G., Y.-N.G., J.-J.G., J.J.Q., Q.J.).ORCID 0000-0001-9834-1214
Second Military Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEndothelial cells (ECs) play a critical role in angiogenesis and vascular remodeling. The heterogeneity of ECs has been reported at adult stages, yet it has not been fully investigated. This study aims to assess the transcriptional heterogeneity of developmental ECs at spatiotemporal level and to reveal the changes of embryonic ECs clustering when endothelium-enriched microRNA-126 (miR-126) was specifically knocked out.

methodsC57BL/6J mice embryos at day 14.5 were harvested and digested, followed by fluorescence-activated cell sorting to enrich ECs. Then, single-cell RNA sequencing was applied to enriched embryonic ECs. Tie2 (Tek receptor tyrosine kinase)-cre-mediated ECs-specific miR-126 knockout mice were constructed, and ECs from Tie2-cre-mediated ECs-specific miR-126 knockout embryos were subjected to single-cell RNA sequencing.

resultsEmbryonic ECs were clustered into 11 groups corresponding to anatomic characteristics. The vascular bed (arteries, capillaries, veins, lymphatics) exhibited transcriptomic similarity across the developmental stage. Embryonic ECs had higher proliferative potential than adult ECs. Integrating analysis showed that 3 ECs populations (hepatic, mesenchymal transition, and pulmonary ECs) were apparently disorganized after miR-126 being knocked out. Gene ontology analysis revealed that disrupted ECs were mainly related to hypoxia, glycometabolism, and vascular calcification. Additionally, in vivo experiment showed that Tie2-cre-mediated ECs-specific miR-126 knockout mice exhibited excessive intussusceptive angiogenesis; reductive glucose and pyruvate tolerance; and excessive accumulation of calcium. Agonist miR-126-3p agomir significantly rescued the phenotype of glucose metabolic dysfunction in Tie2-cre-mediated ECs-specific miR-126 knockout mice.

conclusionsThe heterogeneity of ECs is established as early as the embryonic stage. The deficiency of miR-126 disrupts the differentiation and diversification of embryonic ECs, suggesting that miR-126 plays an essential role in the maintenance of ECs heterogeneity.

Indexed as

AnimalsApoptosisCell HypoxiaCell LineageCell PlasticityCell ProliferationEndothelial CellsGene Expression ProfilingGene Expression Regulation, DevelopmentalGestational AgeGlucoseLiverMetabolic Networks and PathwaysMiceMice, Inbred C57BLMice, KnockoutGlucoseMicroRNAsMIRN126 microRNA, mouseendothelial cellsgene ontologymicemicroRNAtranscriptome

Identifiers

PMID35021856
PMCPMC8860216
OpenAlexW4205913765

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LicenceCC BY-NC-ND
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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.