Evidence map›Paper›PMID 30905619›Full record

ArticleCell stem cell2019

Precise Gene Editing Preserves Hematopoietic Stem Cell Function following Transient p53-Mediated DNA Damage Response.

Giulia Schiroli, Anastasia Conti, Samuele Ferrari, Lucrezia Della Volpe, Aurelien Jacob, Luisa Albano, Stefano Beretta, Andrea Calabria, Valentina Vavassori, Patrizia Gasparini and 9 more

Abstract read
In one paragraph

Article in Cell stem cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 232 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
232citing papers in PubMed, 1 pooled it
14.3field-weighted citation impact, top 1% 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

232 citing papers in PubMed, 1 synthesis or guideline pooled it, 331 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Heterogeneous CRISPR/Cas9 Editing ofInternational journal of molecular sciences · 2026
    Article
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  8. Article
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  14. Article
  15. Article
  16. Gene-sized editing for the therapy of genetic diseases.Functional & integrative genomics · 2026
    Review
  17. Article
  18. Article
  19. Article
  20. Article

172 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 10 institutions in 2 countries.

Giulia SchiroliSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Anastasia ContiSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Samuele FerrariSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.
Lucrezia Della VolpeSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.
Aurelien JacobSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Milano-Bicocca University, 20126 Milan, Italy.
Luisa AlbanoSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Stefano BerettaMilano-Bicocca University, 20126 Milan, Italy; Institute for Biomedical Technologies, National Research Council, 20090 Segrate, Italy.
Andrea CalabriaSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Valentina VavassoriSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy.
Patrizia GaspariniTumor Genomics Unit, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133 Milan, Italy.
Eralda SalatajInserm U1016, Institut Cochin, 75014 Paris, France; CNRS UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, France.
Delphine Ndiaye-LobryInserm U1016, Institut Cochin, 75014 Paris, France; CNRS UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, France.
Chiara BrombinCUSSB-University Center for Statistics in the Biomedical Sciences, Vita-Salute San Raffaele University, 20132 Milan, Italy.
Julie ChaumeilInserm U1016, Institut Cochin, 75014 Paris, France; CNRS UMR8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, France.
Eugenio MontiniSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy.
Ivan MerelliInstitute for Biomedical Technologies, National Research Council, 20090 Segrate, Italy.
Pietro GenoveseSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. Electronic address: genovese.pietro@hsr.it.
Luigi NaldiniSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy; Vita-Salute San Raffaele University, 20132 Milan, Italy. Electronic address: naldini.luigi@hsr.it.
Raffaella Di MiccoSan Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy. Electronic address: dimicco.raffaella@hsr.it.
The San Raffaele Telethon Institute for Gene Therapy · ITIstituto di Ricovero e Cura a Carattere Scientifico San RaffaeleIstituti di Ricovero e Cura a Carattere Scientifico · ITVita-Salute San Raffaele University · ITCentre National de la Recherche Scientifique · FRDélégation Paris 5 · FRFondazione IRCCS Istituto Nazionale dei Tumori · ITInstitut Cochin · FRInstitute of Biomedical Technologies · ITNational Research Council · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Precise gene editing in hematopoietic stem and progenitor cells (HSPCs) holds promise for treating genetic diseases. However, responses triggered by programmable nucleases in HSPCs are poorly characterized and may negatively impact HSPC engraftment and long-term repopulation capacity. Here, we induced either one or several DNA double-stranded breaks (DSBs) with optimized zinc-finger and CRISPR/Cas9 nucleases and monitored DNA damage response (DDR) foci induction, cell-cycle progression, and transcriptional responses in HSPC subpopulations, with up to single-cell resolution. p53-mediated DDR pathway activation was the predominant response to even single-nuclease-induced DSBs across all HSPC subtypes analyzed. Excess DSB load and/or adeno-associated virus (AAV)-mediated delivery of DNA repair templates induced cumulative p53 pathway activation, constraining proliferation, yield, and engraftment of edited HSPCs. However, functional impairment was reversible when DDR burden was low and could be overcome by transient p53 inhibition. These findings provide molecular and functional evidence for feasible and seamless gene editing in HSPCs.

Indexed as

DNA DamageGene EditingAnimalsCell LineHematopoietic Stem CellsHumansK562 CellsMiceMice, Inbred NODMice, KnockoutMice, SCIDTumor Suppressor Protein p53Tumor Suppressor Protein p53adeno-associated vectorDNA damage responseDNA double strand breaksgenome editinghematopoietic stem and progenitor cellsp53 pathwayprogrammable nucleases

Identifiers

PMID30905619
PMCPMC6458988
OpenAlexW2924385776

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.