Evidence map›Paper›PMID 34762852›Full record

ArticleDevelopmental cell2021

1-deoxysphingolipids bind to COUP-TF to modulate lymphatic and cardiac cell development.

Ting Wang, Zheng Wang, Lauriane de Fabritus, Jinglian Tao, Essa M Saied, Ho-Joon Lee, Bulat R Ramazanov, Benjamin Jackson, Daniel Burkhardt, Mikhail Parker and 14 more

Open access · greenAbstract read
In one paragraph

Article in Developmental cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  9. Regulation of cellular and systemic sphingolipid homeostasis.Nature reviews. Molecular cell biology · 2024
    Review
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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

24 authors at 10 institutions in 7 countries.

Ting WangDepartment of Immunobiology, Yale University, New Haven, CT 06520, USA; Department of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, China.
Zheng WangDepartment of Genetics and Cell Biology, Basic Medical College, Qingdao University, Qingdao, Shandong 266071, China; Department of Reproductive Medicine, the Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, China.
Lauriane de FabritusAix-Marseille Universite, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy (CIML), 13288 Marseille Cedex 9, France.
Jinglian TaoDepartment of Hematology, Tianjin Medical University General Hospital, Tianjin 300052, China; Center for Molecular Medicine, Department of Genetics, University of Georgia, Athens, GA 30602, USA.
Essa M SaiedInstitut für Chemie, Humboldt Universität zu Berlin, Berlin 12489, Germany; Chemistry Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt.
Ho-Joon LeeDepartment of Genetics, Yale University, New Haven, CT 06520, USA; Center for Genome Analysis, Yale University, New Haven, CT 06510, USA.
Bulat R RamazanovDepartment of Cell Biology, Yale University, New Haven, CT 06520, USA.
Benjamin JacksonCenter for Molecular Medicine, Department of Genetics, University of Georgia, Athens, GA 30602, USA.
Daniel BurkhardtDepartment of Genetics, Yale University, New Haven, CT 06520, USA.
Mikhail ParkerCenter for Molecular Medicine, Department of Genetics, University of Georgia, Athens, GA 30602, USA.
Anne S GleinichComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Zhirui WangComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Dong Eun SeoCenter for Molecular Medicine, Department of Genetics, University of Georgia, Athens, GA 30602, USA.
Ting ZhouDepartment of Immunobiology, Yale University, New Haven, CT 06520, USA.
Shihao XuNOMIS Center for Immunobiology and Microbial Pathogenesis, the Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Irina AlecuNeural Regeneration Laboratory, Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, Ottawa K1H 8M5, Canada.
Parastoo AzadiComplex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA.
Christoph ArenzInstitut für Chemie, Humboldt Universität zu Berlin, Berlin 12489, Germany.
Thorsten HornemannInstitute of Clinical Chemistry, University and University Hospital of Zurich, Zurich 8091, Switzerland.
Smita KrishnaswamyDepartment of Genetics, Yale University, New Haven, CT 06520, USA.
Serge A van de PavertAix-Marseille Universite, CNRS, INSERM, Centre d'Immunologie de Marseille-Luminy (CIML), 13288 Marseille Cedex 9, France.
Susan M KaechNOMIS Center for Immunobiology and Microbial Pathogenesis, the Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: skaech@salk.edu.
Natalia B IvanovaCenter for Molecular Medicine, Department of Genetics, University of Georgia, Athens, GA 30602, USA. Electronic address: natalia.ivanova@uga.edu.
Fabio R SantoriDepartment of Immunobiology, Yale University, New Haven, CT 06520, USA. Electronic address: fabio.santori@yale.edu.
University of Georgia · USYale University · USHumboldt-Universität zu Berlin · DESalk Institute for Biological Studies · USAffiliated Hospital of Qingdao University · CNAix-Marseille Université · FRCentre d’Immunologie de Marseille-Luminy · FRTianjin Medical University General Hospital · CNUniversity Hospital of Zurich · CHUniversity of Ottawa · CA

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI Reuben Shaw · 1985 to 2026
$82.8M
National Glycoscience Resource- CCRC Service and Training - NGlycoR@CCRCR24GM137782 · NIGMS · UNIVERSITY OF GEORGIA · PI Parastoo Azadi · 2020 to 2026
$5.2M
Novel differentiation repressor module in human ES cellsR01GM107092 · NIGMS · YALE UNIVERSITY · PI IVANOVA, NATALIA B · 2014 to 2022
$2.6M
Discovery of NR4A1/2 ligands controlling tissue-resident memory T (Trm) cellsR21AI131015 · NIAID · YALE UNIVERSITY · PI SANTORI, FABIO RINALDO · 2017 to 2018
$461k
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA014195NIAID NIH HHS R21 AI131015NIGMS NIH HHS R01 GM107092NIGMS NIH HHS R24 GM137782
6 · The paper itself

Abstract

Identification of physiological modulators of nuclear hormone receptor (NHR) activity is paramount for understanding the link between metabolism and transcriptional networks that orchestrate development and cellular physiology. Using libraries of metabolic enzymes alongside their substrates and products, we identify 1-deoxysphingosines as modulators of the activity of NR2F1 and 2 (COUP-TFs), which are orphan NHRs that are critical for development of the nervous system, heart, veins, and lymphatic vessels. We show that these non-canonical alanine-based sphingolipids bind to the NR2F1/2 ligand-binding domains (LBDs) and modulate their transcriptional activity in cell-based assays at physiological concentrations. Furthermore, inhibition of sphingolipid biosynthesis phenocopies NR2F1/2 deficiency in endothelium and cardiomyocytes, and increases in 1-deoxysphingosine levels activate NR2F1/2-dependent differentiation programs. Our findings suggest that 1-deoxysphingosines are physiological regulators of NR2F1/2-mediated transcription.

Indexed as

AnimalsCell DifferentiationGene Expression RegulationHumansLymphatic VesselsMiceOrganogenesisRepressor ProteinsSphingolipids1-deoxysphingolipidRepressor ProteinsSphingolipids1-deoxysphingosinecardiomyocyteCOUP-TFlymphaticmetabolismNR2F1NR2F2NR2F6sphingolipidSPTLC2

Identifiers

PMID34762852
PMCPMC8628544
OpenAlexW3212300774

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.