Evidence map›Paper›PMID 26607381›Full record

ArticleCell stem cell2016

Targeted Application of Human Genetic Variation Can Improve Red Blood Cell Production from Stem Cells.

Felix C Giani, Claudia Fiorini, Aoi Wakabayashi, Leif S Ludwig, Rany M Salem, Chintan D Jobaliya, Stephanie N Regan, Jacob C Ulirsch, Ge Liang, Orna Steinberg-Shemer and 11 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell stem cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
6.6field-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

63 citing papers in PubMed, 86 citations in OpenAlex.

  1. Article
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  6. Multimodal analysis ofbioRxiv : the preprint server for biology · 2025
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  14. Evolution of nanobodies specific for BCL11A.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Article
  16. Article
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  18. Analyses of erythropoiesis from embryonic stem cell-CD34Journal of cellular and molecular medicine · 2022
    Article
  19. Article
  20. Advancing the care of β-thalassaemia patients with novel therapies.Blood transfusion = Trasfusione del sangue · 2022
    Review

3 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

21 authors at 4 institutions in 2 countries.

Felix C Giani *Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Claudia Fiorini *Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Aoi Wakabayashi *Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Leif S LudwigDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Rany M SalemBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Chintan D JobaliyaDepartments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Stephanie N ReganBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jacob C UlirschDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Ge LiangDepartments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Orna Steinberg-ShemerDepartments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Michael H GuoBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Tõnu EskoBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Wei TongDepartments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Carlo BrugnaraDepartment of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Joel N HirschhornBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mitchell J WeissDepartment of Hematology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Leonard I ZonDivision of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Stella T ChouDepartments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Deborah L FrenchDepartments of Pathology and Laboratory Medicine and Pediatrics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kiran MusunuruBroad Institute of MIT and Harvard, Cambridge, MA 02142, 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 · USChildren's Hospital of Philadelphia · USBoston Children's Hospital · USSt. Jude Children's Research Hospital · US

Funding

The Intellectual and Developmental Disabilities Research Center at CHOP/PennU54HD086984 · NICHD · CHILDREN'S HOSP OF PHILADELPHIA · PI YUDKOFF, MARC · 2016 to 2020
$6.3M
Systematic Genetic Dissection of Human ErythropoiesisR01DK103794 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2014 to 2026
$5.9M
Project-002U54DK110805 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI ORKIN, STUART H, ZON, LEONARD IRA · 2016 to 2020
$5.9M
EMBRYONIC HEMATOPOIESISR01HL048801 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ZON, LEONARD IRA · 1992 to 2016
$5.7M
Lnk Regulatory Functions in Hematopoietic Stem CellsR01HL095675 · NHLBI · CHILDREN'S HOSP OF PHILADELPHIA · PI TONG, WEI · 2009 to 2021
$5.6M
Modeling genetic modifiers of hematopoiesis with induced pluripotent stem cellsR01DK100854 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI CHOU, STELLA T · 2014 to 2018
$2.0M
High-throughput screening and stem cell modeling of causal eQTL variantsR01GM104464 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI MUSUNURU, KIRAN · 2013 to 2016
$1.3M
Identifying Genome-wide Association Study-Nominated Regulators of ErythropoiesisR21HL120791 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI SANKARAN, VIJAY GANESH · 2014 to 2015
$477k
Methods for Genetic Association Analysis of Longitudinal and Multiple PhenotypesK99HL122515 · NHLBI · BROAD INSTITUTE, INC. · PI SALEM, RANY · 2014 to 2015
$264k
NHLBI NIH HHS K99 HL122515NHLBI NIH HHS R01 HL048801NHLBI NIH HHS R01 HL095675NHLBI NIH HHS R21 HL120791NICHD NIH HHS U54 HD086984NIDDK NIH HHS R01 DK100854NIDDK NIH HHS R01 DK103794NIDDK NIH HHS U54 DK110805NIGMS NIH HHS R01 GM104464
6 · The paper itself

Abstract

Multipotent and pluripotent stem cells are potential sources for cell and tissue replacement therapies. For example, stem cell-derived red blood cells (RBCs) are a potential alternative to donated blood, but yield and quality remain a challenge. Here, we show that application of insight from human population genetic studies can enhance RBC production from stem cells. The SH2B3 gene encodes a negative regulator of cytokine signaling and naturally occurring loss-of-function variants in this gene increase RBC counts in vivo. Targeted suppression of SH2B3 in primary human hematopoietic stem and progenitor cells enhanced the maturation and overall yield of in-vitro-derived RBCs. Moreover, inactivation of SH2B3 by CRISPR/Cas9 genome editing in human pluripotent stem cells allowed enhanced erythroid cell expansion with preserved differentiation. Our findings therefore highlight the potential for combining human genome variation studies with genome editing approaches to improve cell and tissue production for regenerative medicine.

Indexed as

Cell DifferentiationCRISPR-Cas SystemsCytokinesEmbryonic Stem CellsErythrocytesFetal BloodGenetic TechniquesGenetic VariationGenome, HumanHematopoietic Stem CellsHemoglobinsHumansMutationPluripotent Stem CellsRegenerative MedicineStem CellsCytokinesHemoglobins

Identifiers

PMID26607381
PMCPMC4707983
OpenAlexW1811026913

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.