Evidence map›Paper›PMID 32877675›Full record

ArticleCell reports2020

Controlled Cycling and Quiescence Enables Efficient HDR in Engraftment-Enriched Adult Hematopoietic Stem and Progenitor Cells.

Jiyung J Shin, Markus S Schröder, Francisco Caiado, Stacia K Wyman, Nicolas L Bray, Matteo Bordi, Mark A Dewitt, Jonathan T Vu, Won-Tae Kim, Dirk Hockemeyer and 2 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

61 citing papers in PubMed, 87 citations in OpenAlex.

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  13. A differentiated β-globin gene replacement strategy uses heterologous introns to restore physiological expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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1 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

12 authors at 4 institutions in 2 countries.

Jiyung J ShinInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Department of Biology, ETH Zürich, 8093 Zürich, Switzerland.
Markus S SchröderDepartment of Biology, ETH Zürich, 8093 Zürich, Switzerland.
Francisco CaiadoDepartment of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, 8091 Zurich, Switzerland.
Stacia K WymanInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Nicolas L BrayInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Matteo BordiDepartment of Biology, ETH Zürich, 8093 Zürich, Switzerland.
Mark A DewittInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Jonathan T VuInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Won-Tae KimDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Dirk HockemeyerDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Markus G ManzDepartment of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, 8091 Zurich, Switzerland.
Jacob E CornInnovative Genomics Institute, University of California, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA; Department of Biology, ETH Zürich, 8093 Zürich, Switzerland. Electronic address: jacob.corn@biol.ethz.ch.
ETH Zurich · CHInnovative Genomics Institute · USUniversity of California, Berkeley · USUniversity of Zurich · CH

Funding

Training in Basic Research on Aging and Age-Related DiseaseT32AG000266 · NIA · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Lisa M Ellerby · 1998 to 2026
$13.8M
Discovering mechanisms that regulate organelle autophagyDP2HL141006 · NHLBI · UNIVERSITY OF CALIFORNIA BERKELEY · PI CORN, JACOB ELLERY · 2017 to 2017
$2.4M
NHLBI NIH HHS DP2 HL141006NIA NIH HHS T32 AG000266
6 · The paper itself

Abstract

Genome editing often takes the form of either error-prone sequence disruption by non-homologous end joining (NHEJ) or sequence replacement by homology-directed repair (HDR). Although NHEJ is generally effective, HDR is often difficult in primary cells. Here, we use a combination of immunophenotyping, next-generation sequencing, and single-cell RNA sequencing to investigate and reprogram genome editing outcomes in subpopulations of adult hematopoietic stem and progenitor cells. We find that although quiescent stem-enriched cells mostly use NHEJ, non-quiescent cells with the same immunophenotype use both NHEJ and HDR. Inducing quiescence before editing results in a loss of HDR in all cell subtypes. We develop a strategy of controlled cycling and quiescence that yields a 6-fold increase in the HDR/NHEJ ratio in quiescent stem cells ex vivo and in vivo. Our results highlight the tension between editing and cellular physiology and suggest strategies to manipulate quiescent cells for research and therapeutic genome editing.

Indexed as

CRISPR-Cas SystemsGATA3 Transcription FactorGene EditingGenetic TherapyHematopoietic Stem CellsHumansRecombinational DNA RepairStem CellsGATA3 protein, humanGATA3 Transcription Factoradult hematopoietic stem cellscell cycleCRISPRgene editinggene therapyhomology-directed repairquiescence

Identifiers

PMID32877675
PMCPMC7487781
OpenAlexW3082828501

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.