Evidence map›Paper›PMID 20089964›Full record

ArticleBlood2010

Knockdown of Fanconi anemia genes in human embryonic stem cells reveals early developmental defects in the hematopoietic lineage.

Asmin Tulpule, M William Lensch, Justine D Miller, Karyn Austin, Alan D'Andrea, Thorsten M Schlaeger, Akiko Shimamura, George Q Daley

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% 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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. International journal of biological sciences · 2023
    Article
  5. Review
  6. Article
  7. Review
  8. Fanconi anemia and the underlying causes of genomic instability.Environmental and molecular mutagenesis · 2020
    Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Pluripotent stem cells in disease modelling and drug discovery.Nature reviews. Molecular cell biology · 2016
    Review
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 1 country.

Asmin TulpuleStem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute, MA, USA.
M William Lensch
Justine D Miller
Karyn Austin
Alan D'Andrea
Thorsten M Schlaeger
Akiko Shimamura
George Q Daley
Harvard Stem Cell Institute · USDana-Farber Cancer Institute · USHarvard University · USSeattle Children's Hospital · US

Funding

Human Pluripotent Stem Cell and Progenitor Models of Cardiac and Blood DiseasesU01HL100001 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI DALEY, GEORGE Q, ORKIN, STUART H · 2009 to 2015
$8.9M
NIH Director's Pioneer Award (RMI)DP1OD000256 · OD · CHILDREN'S HOSPITAL BOSTON · PI DALEY, GEORGE Q · 2004 to 2008
$4.2M
Shwachman-Diamond Syndrome: Molecular PathogenesisR01HL079582 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI SHIMAMURA, AKIKO · 2004 to 2012
$3.7M
Howard Hughes Medical InstituteNHLBI NIH HHS R01 HL079582NHLBI NIH HHS U01 HL100001NIH HHS DP1 OD000256
6 · The paper itself

Abstract

Fanconi anemia (FA) is a genetically heterogeneous, autosomal recessive disorder characterized by pediatric bone marrow failure and congenital anomalies. The effect of FA gene deficiency on hematopoietic development in utero remains poorly described as mouse models of FA do not develop hematopoietic failure and such studies cannot be performed on patients. We have created a human-specific in vitro system to study early hematopoietic development in FA using a lentiviral RNA interference (RNAi) strategy in human embryonic stem cells (hESCs). We show that knockdown of FANCA and FANCD2 in hESCs leads to a reduction in hematopoietic fates and progenitor numbers that can be rescued by FA gene complementation. Our data indicate that hematopoiesis is impaired in FA from the earliest stages of development, suggesting that deficiencies in embryonic hematopoiesis may underlie the progression to bone marrow failure in FA. This work illustrates how hESCs can provide unique insights into human development and further our understanding of genetic disease.

Indexed as

Fanconi Anemia Complementation Group A ProteinFanconi Anemia Complementation Group D2 ProteinGene Knockdown TechniquesBone MarrowCell LineEmbryonic Stem CellsFanconi AnemiaHematopoiesisHematopoietic Stem CellsHumansModels, BiologicalRNA InterferenceFANCA protein, humanFANCD2 protein, humanFanconi Anemia Complementation Group A ProteinFanconi Anemia Complementation Group D2 Protein

Identifiers

PMID20089964
PMCPMC2867260
OpenAlexW2069111817

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.