Evidence map›Paper›PMID 25498912›Full record

ArticleBlood2015

ST3Gal-4 is the primary sialyltransferase regulating the synthesis of E-, P-, and L-selectin ligands on human myeloid leukocytes.

Nandini Mondal, Alexander Buffone, Gino Stolfa, Aristotelis Antonopoulos, Joseph T Y Lau, Stuart M Haslam, Anne Dell, Sriram Neelamegham

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 10% 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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.

  1. Pooled it
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  12. Spatially ResolvedbioRxiv : the preprint server for biology · 2024
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5 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

8 authors at 3 institutions in 2 countries.

Nandini MondalDepartment of Chemical and Biological Engineering and The New York State Center for Excellence in Bioinformatics and Life Sciences, State University of New York, Buffalo, NY;
Alexander BuffoneDepartment of Chemical and Biological Engineering and The New York State Center for Excellence in Bioinformatics and Life Sciences, State University of New York, Buffalo, NY;
Gino StolfaDepartment of Chemical and Biological Engineering and The New York State Center for Excellence in Bioinformatics and Life Sciences, State University of New York, Buffalo, NY;
Aristotelis AntonopoulosDepartment of Life Sciences, Imperial College London, London, United Kingdom; and.
Joseph T Y LauMolecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, NY.
Stuart M HaslamDepartment of Life Sciences, Imperial College London, London, United Kingdom; and.
Anne DellDepartment of Life Sciences, Imperial College London, London, United Kingdom; and.
Sriram NeelameghamDepartment of Chemical and Biological Engineering and The New York State Center for Excellence in Bioinformatics and Life Sciences, State University of New York, Buffalo, NY;
University at Buffalo, State University of New York · USImperial College London · GBRoswell Park Comprehensive Cancer Center · US

Funding

Two-Spirit Films in Indigenous Cancer HealthP30CA016056 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI MARK G FRATTINI · 1985 to 2026
$116.6M
REGULATION OF LACTOSAMINYL GLYCAN BIOSYNTHESIS IN HEMATOPOIETIC CELLSP01HL107146 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SACKSTEIN, ROBERT · 2011 to 2017
$17.7M
Systems Biology of GlycosylationR01HL103411 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM · 2011 to 2025
$7.1M
SELECTIN MEDIATED CELL ADHESION UNDER HYDRODYNAMIC SHEARR01HL063014 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI NEELAMEGHAM, SRIRAM · 2001 to 2014
$3.0M
Biotechnology and Biological Sciences Research Council BB/K016164/1NCI NIH HHS P30 CA016056NHLBI NIH HHS HL103411NHLBI NIH HHS HL107146NHLBI NIH HHS HL63014NHLBI NIH HHS P01 HL107146NHLBI NIH HHS R01 HL063014NHLBI NIH HHS R01 HL103411
6 · The paper itself

Abstract

The precise glycosyltransferase enzymes that mediate selectin-ligand biosynthesis in human leukocytes are unknown. This knowledge is important because selectin-mediated cell tethering and rolling is a critical component of both normal immune response and various vascular disorders. We evaluated the role of 3 α(2,3)sialyltransferases, ST3Gal-3, -4, and -6, which act on the type II N-Acetyllactosamine structure (Galβ1,4GlcNAc) to create sialyl Lewis-X (sLe(X)) and related sialofucosylated glycans on human leukocytes of myeloid lineage. These genes were either silenced using lentiviral short hairpin RNA (shRNA) or functionally ablated using the clustered regularly interspaced short palindromic repeat/Cas9 technology. The results show that ST3Gal-4, but not ST3Gal-3 or -6, is the major sialyltransferase regulating the biosynthesis of E-, P-, and L-selectin ligands in humans. Reduction in ST3Gal-4 activity lowered cell-surface HECA-452 epitope expression by 75% to 95%. Glycomics profiling of knockouts demonstrate an almost complete loss of the sLe(X) epitope on both leukocyte N- and O-glycans. In cell-adhesion studies, ST3Gal-4 knockdown/knockout cells displayed 90% to 100% reduction in tethering and rolling density on all selectins. ST3Gal-4 silencing in neutrophils derived from human CD34(+) hematopoietic stem cells also resulted in 80% to 90% reduction in cell adhesion to all selectins. Overall, a single sialyltransferase regulates selectin-ligand biosynthesis in human leukocytes, unlike mice where multiple enzymes contribute to this function.

Indexed as

Animalsbeta-Galactoside alpha-2,3-SialyltransferaseCell AdhesionCHO CellsCricetinaeCricetulusE-SelectinGene SilencingGlycomicsHematopoietic Stem CellsHL-60 CellsHumansLeukocyte RollingL-SelectinMiceNeutrophilsbeta-Galactoside alpha-2,3-SialyltransferaseE-SelectinL-SelectinP-SelectinSialyltransferases

Identifiers

PMID25498912
PMCPMC4304113
OpenAlexW1995555888

What OpenQuestion holds

Textmetadata
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.