Evidence map›Paper›PMID 27458028›Full record

ArticleScientific reports2016

Using CRISPR-Cas9 to quantify the contributions of O-glycans, N-glycans and Glycosphingolipids to human leukocyte-endothelium adhesion.

Gino Stolfa, Nandini Mondal, Yuqi Zhu, Xinheng Yu, Alexander Buffone, Sriram Neelamegham

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
3.5field-weighted citation impact, top 7% 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

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Gino StolfaDepartment of Chemical &Biological Engineering and Clinical &Translational Research Center, State University of New York, Buffalo, NY 14260, USA.
Nandini MondalDepartment of Chemical &Biological Engineering and Clinical &Translational Research Center, State University of New York, Buffalo, NY 14260, USA.
Yuqi ZhuDepartment of Chemical &Biological Engineering and Clinical &Translational Research Center, State University of New York, Buffalo, NY 14260, USA.
Xinheng YuDepartment of Chemical &Biological Engineering and Clinical &Translational Research Center, State University of New York, Buffalo, NY 14260, USA.
Alexander BuffoneDepartment of Chemical &Biological Engineering and Clinical &Translational Research Center, State University of New York, Buffalo, NY 14260, USA.
Sriram NeelameghamDepartment of Chemical &Biological Engineering and Clinical &Translational Research Center, State University of New York, Buffalo, NY 14260, USA.
University at Buffalo, State University of New York · US

Funding

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
NHLBI NIH HHS R01 HL063014NHLBI NIH HHS R01 HL103411
6 · The paper itself

Abstract

There is often interest in dissecting the relative contributions of the N-glycans, O-glycans and glycosphingolipids (GSLs) in regulating complex biological traits like cell signaling, adhesion, development and metastasis. To address this, we developed a CRISPR-Cas9 toolkit to selectively truncate each of these commonly expressed glycan-types. Here, O-glycan biosynthesis was truncated by knocking-out Core 1 β3Gal-T Specific Molecular Chaperone (COSMC), N-glycans by targeting the β1,2 GlcNAc-transferase (MGAT1) and GSLs by deleting UDP-glucose ceramide glucosyltransferase (UGCG). These reagents were applied to reveal the glycoconjugates regulating human myeloid cell adhesion to selectins under physiological shear-flow observed during inflammation. These functional studies show that leukocyte rolling on P- and L-selectin is ablated in cells lacking O-glycans, with N-glycan truncation also increasing cell rolling velocity on L-selectin. All three glycan families contributed to E-selectin dependent cell adhesion with N-glycans contributing to all aspects of the leukocyte adhesion cascade, O-glycans only being important during initial recruitment, and GSLs stabilizing slow cell rolling and the transition to firm arrest. Overall, the genome editing tools developed here may be broadly applied in studies of cellular glycosylation.

Indexed as

Cell AdhesionCell Line, TumorCRISPR-Cas SystemsGlucosyltransferasesGlycosphingolipidsHumansHuman Umbilical Vein Endothelial CellsLeukocytesN-AcetylglucosaminyltransferasesPolysaccharidesSelectinsceramide glucosyltransferaseGlucosyltransferasesGlycosphingolipidsMGAT1 protein, humanN-AcetylglucosaminyltransferasesPolysaccharidesSelectins

Identifiers

PMID27458028
PMCPMC4960646
OpenAlexW2480722975

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.