Evidence map›Paper›PMID 28283060›Full record

ArticleCell2017

Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling.

Chia Chi M Ho, Akanksha Chhabra, Philipp Starkl, Peter-John Schnorr, Stephan Wilmes, Ignacio Moraga, Hye-Sook Kwon, Nicolas Gaudenzio, Riccardo Sibilano, Tom S Wehrman and 9 more

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

Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

48 citing papers in PubMed, 78 citations in OpenAlex.

  1. Article
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  9. Influences on the Hematopoietic Stem Cell Niche.SciBase hematology & blood disorders · 2024
    Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. KIT as a master regulator of the mast cell lineage.The Journal of allergy and clinical immunology · 2022
    Review
  17. Article
  18. Article
  19. Article
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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

19 authors at 8 institutions in 4 countries.

Chia Chi M HoDepartment of Bioengineering, Stanford University School of Engineering, 443 Via Ortega, Stanford, CA 94305, USA; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
Akanksha ChhabraDepartment of Blood and Marrow Transplantation, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
Philipp StarklDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Medicine I, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Peter-John SchnorrDepartment of Blood and Marrow Transplantation, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
Stephan WilmesDepartment of Biology, University of Osnabruck, Barbarastr. 11, 49076 Osnabruck, Germany.
Ignacio MoragaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA.
Hye-Sook KwonDepartment of Blood and Marrow Transplantation, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
Nicolas GaudenzioDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Riccardo SibilanoDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Tom S WehrmanPrimity Bio, 48383 Fremont Blvd, Suite 118, Fremont, CA 94538, USA.
Milica GakovicDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA.
Jonathan T SockoloskyDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA.
Matthew R TiffanyDepartment of Pediatrics and Genetics, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Aaron M RingDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA.
Jacob PiehlerDepartment of Biology, University of Osnabruck, Barbarastr. 11, 49076 Osnabruck, Germany.
Irving L WeissmanDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
Stephen J GalliDepartment of Pathology, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Department of Microbiology and Immunology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA.
Judith A ShizuruDepartment of Blood and Marrow Transplantation, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
K Christopher GarciaDepartment of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA; Department of Structural Biology, Stanford University School of Medicine, 299 Campus Drive, Stanford, CA 94305, USA; Howard Hughes Medical Institute, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA. Electronic address: kcgarcia@stanford.edu.
Stanford University · USCancer Institute (WIA) · INStanford Medicine · USHochschule Osnabrück · DEStanford Cancer InstituteInstitute for Stem Cell Biology and Regenerative Medicine · INMedical University of Vienna · ATPrimity Bio (United States) · US

Funding

Structure, function and engineering of immune cytokine receptor signalingR37AI051321 · NIAID · STANFORD UNIVERSITY · PI GARCIA, KENAN CHRISTOPHER · 2013 to 2022
$4.2M
Strategies for Receptor inhibition in immunotherapyR01CA177684 · NCI · STANFORD UNIVERSITY · PI DOUGAN, MICHAEL LAWRENCE, GARCIA, KENAN CHRISTOPHER · 2014 to 2025
$3.5M
Enhancing the immune response to antigens delivered by the bacterial vector, StreR43AI072905 · NIAID · SIGA TECHNOLOGIES, INC. · PI HRUBY, DENNIS E. · 2007 to 2008
$554k
Howard Hughes Medical InstituteNCI NIH HHS R01 CA177684NIAID NIH HHS R37 AI051321NIAID NIH HHS R43 AI072905
6 · The paper itself

Abstract

Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude. This SCF variant elicited biased activation of hematopoietic progenitors over mast cells in vitro and in vivo. Mouse models of SCF-mediated anaphylaxis, radioprotection, and hematopoietic expansion revealed that this SCF partial agonist retained therapeutic efficacy while exhibiting virtually no anaphylactic off-target effects. The approach of biasing cell activation by tuning signaling thresholds and outputs has applications to many dimeric receptor-ligand systems.

Indexed as

Signal TransductionAnaphylaxisAnimalsDimerizationHematopoietic Stem CellsHumansMast CellsMiceMice, Inbred C57BLModels, MolecularProtein EngineeringProto-Oncogene Proteins c-kitStem Cell FactorProto-Oncogene Proteins c-kitStem Cell Factoranaphylaxisc-Kitcytokinehematopoietic stem cellsmast cellspleiotropyprotein engineeringreceptor signalingreceptor tyrosine kinasestem cell factor

Identifiers

PMID28283060
PMCPMC5526607
OpenAlexW2593639501

What OpenQuestion holds

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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.