Evidence map›Paper›PMID 37137305›Full record

ArticleCell2023

Massively parallel base editing to map variant effects in human hematopoiesis.

Jorge D Martin-Rufino, Nicole Castano, Michael Pang, Emanuelle I Grody, Samantha Joubran, Alexis Caulier, Lara Wahlster, Tongqing Li, Xiaojie Qiu, Anna Maria Riera-Escandell and 15 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed
18.3field-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

91 citing papers in PubMed, 119 citations in OpenAlex.

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  19. Scaling perturbations: beyond genome-scale CRISPR screens.bioRxiv : the preprint server for biology · 2026
    Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 6 institutions in 2 countries.

Jorge D Martin-RufinoDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; PhD Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
Nicole CastanoDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Michael PangDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard-MIT Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA.
Emanuelle I GrodyBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Samantha JoubranDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Chemical Biology PhD Program, Harvard Medical School, Boston, MA 02115, USA.
Alexis CaulierDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Lara WahlsterDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tongqing LiDepartment of Pharmacology and Yale Cancer Biology Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Xiaojie QiuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Anna Maria Riera-EscandellIndependent Researcher, now at Google, Zurich, Switzerland.
Gregory A NewbyBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Aziz Al'KhafajiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Santosh ChaudharyBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Susan BlackDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Chen WengDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Glen MunsonBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
David R LiuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
Marcin W WlodarskiDepartment of Hematology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Kacie SimsSt. Jude Affiliate Clinic at Our Lady of the Lake Children's Health, Baton Rouge, LA 70809, USA.
Jamie H OakleyAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, GA 30322, USA.
Ross M FasanoAflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University, Atlanta, GA 30322, USA.
Ramnik J XavierBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for Computational and Integrative Biology, Department of Molecular Biology, and Center for the Study of Inflammatory Bowel Disease, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Eric S LanderBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daryl E KleinDepartment of Pharmacology and Yale Cancer Biology Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
Vijay G SankaranDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: sankaran@broadinstitute.org.
Broad Institute · USEmory University · USYale Cancer Center · USGoogle (Switzerland) · CHOur Lady of the Lake Children's Hospital · USSt. Jude Children's Research Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Center for Genomic Editing and Recording: Development and Application of Next-Generation Genome and Epigenome Editing Methods to Advance the Study and Treatment of Human DiseaseRM1HG009490 · NHGRI · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · PI Brittany S. Adamson, Martin Joseph Ankrah Aryee · 2017 to 2026
$22.7M
Stem Cell and Transplantation BiologyU54DK106829 · NIDDK · FRED HUTCHINSON CANCER RESEARCH CENTER · PI DEREK L STIREWALT · 2015 to 2026
$9.1M
Integrating Chemistry and Evolution to Illuminate Biology and Enable Novel TherapeuticsR35GM118062 · NIGMS · HARVARD UNIVERSITY · PI LIU, DAVID R · 2016 to 2025
$6.4M
Systematic Genetic Dissection of Human ErythropoiesisR01DK103794 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2014 to 2026
$5.9M
Next generation functional genomics of hematology traitsR01HL146500 · NHLBI · UNIVERSITY OF WASHINGTON · PI ALEXANDER P REINER · 2020 to 2026
$5.7M
Selective pressures from inherited variation impacting myeloproliferative neoplasm initiationR01CA265726 · NCI · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2022 to 2026
$2.5M
Expanding the Scope of Base EditingU01AI142756 · NIAID · BROAD INSTITUTE, INC. · PI LIU, DAVID R · 2018 to 2022
$2.1M
In vivo precision genome editing to correct genetic diseaseK99HL163805 · NHLBI · BROAD INSTITUTE, INC. · PI NEWBY, GREGORY A. · 2022 to 2022
$167k
NCI NIH HHS R01 CA265726NHGRI NIH HHS RM1 HG009490NHLBI NIH HHS K99 HL163805NHLBI NIH HHS R01 HL146500NIAID NIH HHS U01 AI142756NIDDK NIH HHS P30 DK043351NIDDK NIH HHS R01 DK103794NIDDK NIH HHS U54 DK106829NIGMS NIH HHS R35 GM118062
6 · The paper itself

Abstract

Systematic evaluation of the impact of genetic variants is critical for the study and treatment of human physiology and disease. While specific mutations can be introduced by genome engineering, we still lack scalable approaches that are applicable to the important setting of primary cells, such as blood and immune cells. Here, we describe the development of massively parallel base-editing screens in human hematopoietic stem and progenitor cells. Such approaches enable functional screens for variant effects across any hematopoietic differentiation state. Moreover, they allow for rich phenotyping through single-cell RNA sequencing readouts and separately for characterization of editing outcomes through pooled single-cell genotyping. We efficiently design improved leukemia immunotherapy approaches, comprehensively identify non-coding variants modulating fetal hemoglobin expression, define mechanisms regulating hematopoietic differentiation, and probe the pathogenicity of uncharacterized disease-associated variants. These strategies will advance effective and high-throughput variant-to-function mapping in human hematopoiesis to identify the causes of diverse diseases.

Indexed as

Gene EditingHematopoietic Stem CellsCell DifferentiationCRISPR-Cas SystemsGenetic EngineeringGenomeHematopoiesisHumansSingle-Cell Analysisbase editingdifferentiationfunctional screensgenome engineeringhematopoiesishematopoietic stem cellprimary cellssingle-cell genomics

Identifiers

PMID37137305
PMCPMC10225359
OpenAlexW4367692380

What OpenQuestion holds

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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.