Evidence map›Paper›PMID 28481220›Full record

ArticleThe Journal of clinical investigation2017

mRNA-mediated glycoengineering ameliorates deficient homing of human stem cell-derived hematopoietic progenitors.

Jungmin Lee, Brad Dykstra, Joel A Spencer, Laurie L Kenney, Dale L Greiner, Leonard D Shultz, Michael A Brehm, Charles P Lin, Robert Sackstein, Derrick J Rossi

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.5field-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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Review
  2. Review
  3. The biology of E-selectin ligands in leukemogenesis.Advances in cancer research · 2023
    Review
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
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  11. Article
  12. Article
  13. Humanized mice in studying efficacy and mechanisms of PD-1-targeted cancer immunotherapy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018
    Article
  14. Transfection with CXCR4 potentiates homing of mesenchymal stem cellsInternational journal of ophthalmology · 2018
    Article
  15. Article
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

10 authors at 5 institutions in 1 country.

Jungmin LeeProgram in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Brad DykstraDepartment of Dermatology, Brigham and Women's Hospital, and.
Joel A SpencerAdvanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, and.
Laurie L KenneyThe University of Massachusetts Medical School, Department of Molecular Medicine, Diabetes Center of Excellence, Worcester, Massachusetts, USA.
Dale L GreinerThe University of Massachusetts Medical School, Department of Molecular Medicine, Diabetes Center of Excellence, Worcester, Massachusetts, USA.
Leonard D ShultzThe Jackson Laboratory, Bar Harbor, Maine, USA.
Michael A BrehmThe University of Massachusetts Medical School, Department of Molecular Medicine, Diabetes Center of Excellence, Worcester, Massachusetts, USA.
Charles P LinAdvanced Microscopy Program, Center for Systems Biology and Wellman Center for Photomedicine, and.
Robert SacksteinDepartment of Dermatology, Brigham and Women's Hospital, and.
Derrick J RossiProgram in Cellular and Molecular Medicine, Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Brigham and Women's Hospital · USHarvard University · USCenter for Systems Biology · USJackson Laboratory · USMassachusetts General Hospital · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI William Carl Skarnes · 1985 to 2026
$61.9M
Progenitor Cell Biology Consortium Administrative Coordinating CenterU01HL099997 · NHLBI · UNIVERSITY OF MARYLAND BALTIMORE · PI TERRIN, MICHAEL L · 2009 to 2015
$29.9M
REGULATION OF LACTOSAMINYL GLYCAN BIOSYNTHESIS IN HEMATOPOIETIC CELLSP01HL107146 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SACKSTEIN, ROBERT · 2011 to 2017
$17.7M
Preclinical development of gene-edited human hematopoietic stem cellsU19HL129903 · NHLBI · HARVARD UNIVERSITY · PI SCADDEN, DAVID T · 2015 to 2019
$11.5M
Integrating lipid genotyes and phenotypes in iPS derived hepatocytes/adipocytesU01HL107440 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI COWAN, CHAD ALBERT, DEO, RAHUL CHANDRAKANT · 2011 to 2015
$9.0M
Humanized Mouse Avatars for T1DUC4DK104218 · NIDDK · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BREHM, MICHAEL ALLEN, DALEY, GEORGE Q · 2014 to 2014
$4.1M
Development and Validation of Novel NSG Mouse Models for Human Stem Cell TherapyR24OD018259 · OD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BREHM, MICHAEL ALLEN, GREINER, DALE LESLIE · 2014 to 2017
$3.0M
Multi-wavelength femtosecond laser sources for intravital multiphoton microscopyR01EB017274 · NIBIB · CORNELL UNIVERSITY · PI LIN, CHARLES P., XU, CHRIS · 2013 to 2016
$2.6M
Reprogramming committed blood cells to a hematopoietic stem cell fateR01HL107630 · NHLBI · IMMUNE DISEASE INSTITUTE, INC. · PI ROSSI, DERRICK J. · 2011 to 2015
$2.5M
Stem Cell Engagement of the NicheR01HL097794 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI SCADDEN, DAVID T · 2009 to 2012
$2.4M
NCI NIH HHS P30 CA034196NHLBI NIH HHS P01 HL107146NHLBI NIH HHS R01 HL097794NHLBI NIH HHS R01 HL107630NHLBI NIH HHS U01 HL099997NHLBI NIH HHS U01 HL107440NHLBI NIH HHS U19 HL129903NIBIB NIH HHS R01 EB017274NIDDK NIH HHS UC4 DK104218NIH HHS R24 OD018259
6 · The paper itself

Abstract

Generation of functional hematopoietic stem and progenitor cells (HSPCs) from human pluripotent stem cells (PSCs) has been a long-sought-after goal for use in hematopoietic cell production, disease modeling, and eventually transplantation medicine. Homing of HSPCs from bloodstream to bone marrow (BM) is an important aspect of HSPC biology that has remained unaddressed in efforts to derive functional HSPCs from human PSCs. We have therefore examined the BM homing properties of human induced pluripotent stem cell-derived HSPCs (hiPS-HSPCs). We found that they express molecular effectors of BM extravasation, such as the chemokine receptor CXCR4 and the integrin dimer VLA-4, but lack expression of E-selectin ligands that program HSPC trafficking to BM. To overcome this deficiency, we expressed human fucosyltransferase 6 using modified mRNA. Expression of fucosyltransferase 6 resulted in marked increases in levels of cell surface E-selectin ligands. The glycoengineered cells exhibited enhanced tethering and rolling interactions on E-selectin-bearing endothelium under flow conditions in vitro as well as increased BM trafficking and extravasation when transplanted into mice. However, glycoengineered hiPS-HSPCs did not engraft long-term, indicating that additional functional deficiencies exist in these cells. Our results suggest that strategies toward increasing E-selectin ligand expression could be applicable as part of a multifaceted approach to optimize the production of HSPCs from human PSCs.

Indexed as

Cell MovementAnimalsCell DifferentiationCells, CulturedCoculture TechniquesE-SelectinFucosyltransferasesGlycosylationHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHumansInduced Pluripotent Stem CellsMice, Inbred NODMice, SCIDRNA, MessengerRNA Processing, Post-TranscriptionalE-SelectinFucosyltransferasesFUT6 protein, humanRNA, MessengerSELE protein, human

Identifiers

PMID28481220
PMCPMC5451245
OpenAlexW2611387697

What OpenQuestion holds

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Read underepoch 390

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.