Evidence map›Paper›PMID 36055241›Full record

ArticleStem cell reports2022

Whole-genome CRISPR screening identifies genetic manipulations to reduce immune rejection of stem cell-derived islets.

Elad Sintov, Igor Nikolskiy, Victor Barrera, Jennifer Hyoje-Ryu Kenty, Alexander S Atkin, Dario Gerace, Shannan J Ho Sui, Kyle Boulanger, Douglas A Melton

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

Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
8.5field-weighted citation impact, top 2% 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

29 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
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  4. Article
  5. From bats to humans: uncoveringbioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Review
  8. Review
  9. Engineering hypoimmune stem cell-derived beta cells.Stem cell research & therapy · 2025
    Review
  10. Review
  11. Review
  12. Islet Cell Replacement and Regeneration for Type 1 Diabetes: Current Developments and Future Prospects.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025
    Review
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  15. Review
  16. Review
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  20. Applications of Genome-Editing Technologies for Type 1 Diabetes.International journal of molecular sciences · 2023
    Review
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

9 authors at 2 institutions in 1 country.

Elad SintovDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA. Electronic address: sintov@fas.harvard.edu.
Igor NikolskiyDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Victor BarreraBioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Jennifer Hyoje-Ryu KentyDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Alexander S AtkinDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Dario GeraceDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Shannan J Ho SuiBioinformatics Core, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Kyle BoulangerDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA.
Douglas A MeltonDepartment of Stem Cell and Regenerative Biology, Harvard Stem Cell Institute, Harvard University, Cambridge, MA, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: dmelton@harvard.edu.
Harvard University · USHoward Hughes Medical Institute · US

Funding

The Harvard Clinical and Translational Science CenterUL1TR002541 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2018 to 2022
$93.0M
Howard Hughes Medical InstituteNCATS NIH HHS UL1 TR002541
6 · The paper itself

Abstract

Human embryonic stem cells (hESCs) provide opportunities for cell replacement therapy of insulin-dependent diabetes. Therapeutic quantities of human stem cell-derived islets (SC-islets) can be produced by directed differentiation. However, preventing allo-rejection and recurring autoimmunity, without the use of encapsulation or systemic immunosuppressants, remains a challenge. An attractive approach is to transplant SC-islets, genetically modified to reduce the impact of immune rejection. To determine the underlying forces that drive immunogenicity of SC-islets in inflammatory environments, we performed single-cell RNA sequencing (scRNA-seq) and whole-genome CRISPR screen of SC-islets under immune interaction with allogeneic peripheral blood mononuclear cells (PBMCs). Data analysis points to "alarmed" populations of SC-islets that upregulate genes in the interferon (IFN) pathway. The CRISPR screen in vivo confirms that targeting IFNγ-induced mediators has beneficial effects on SC-islet survival under immune attack. Manipulating the IFN response by depleting chemokine ligand 10 (CXCL10) in SC-islet grafts confers improved survival against allo-rejection compared with wild-type grafts in humanized mice. These results offer insights into the nature of immune destruction of SC-islets during allogeneic responses and provide targets for gene editing.

Indexed as

Human Embryonic Stem CellsIslets of LangerhansIslets of Langerhans TransplantationAnimalsClustered Regularly Interspaced Short Palindromic RepeatsHumansLeukocytes, MononuclearMicebeta cellschemokineCXCL10diabeteshypo-immunogenicityimmunogenicitypancreatic isletsT1Dtransplantation

Identifiers

PMID36055241
PMCPMC9481918
OpenAlexW4294190626

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.