Evidence map›Paper›PMID 22806889›Full record

ArticleBlood2012

MKL1 and MKL2 play redundant and crucial roles in megakaryocyte maturation and platelet formation.

Elenoe C Smith, Jonathan N Thon, Matthew T Devine, Sharon Lin, Vincent P Schulz, Yanwen Guo, Stephanie A Massaro, Stephanie Halene, Patrick Gallagher, Joseph E Italiano and 1 more

Open access · greenAbstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

38 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
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  11. MRTFB suppresses colorectal cancer development through regulating SPDL1 and MCAM.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  12. Review
  13. Article
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  15. Review
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  17. Review
  18. Serum Response Factor Is Essential for Maintenance of Podocyte Structure and Function.Journal of the American Society of Nephrology : JASN · 2018
    Article
  19. Article
  20. Article
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

11 authors at 3 institutions in 1 country.

Elenoe C SmithDepartment of Cell Biology, Yale University School of Medicine, New Haven, CT, USA.
Jonathan N Thon
Matthew T Devine
Sharon Lin
Vincent P Schulz
Yanwen Guo
Stephanie A Massaro
Stephanie Halene
Patrick Gallagher
Joseph E Italiano
Diane S Krause
Brigham and Women's Hospital · USPediatrics and Genetics · USYale University · US

Funding

Yale Center of Excellence in Molecular HematologyP30DK072442 · NIDDK · YALE UNIVERSITY · PI KRAUSE, DIANE S · 2005 to 2010
$5.2M
Barrier Insulators in ErythropoiesisR01HL106184 · NHLBI · YALE UNIVERSITY · PI GALLAGHER, PATRICK G · 2011 to 2014
$1.6M
MKL in megakaryocytopoiesisR01DK086267 · NIDDK · YALE UNIVERSITY · PI KRAUSE, DIANE S · 2010 to 2013
$1.5M
Effect of MKL1 on murine embryonic megakaryocytopoiesisF31HL094118 · NHLBI · YALE UNIVERSITY · PI SMITH, ELENOE C. · 2008 to 2010
$124k
NHLBI NIH HHS F31 HL 094118NHLBI NIH HHS F31 HL094118NHLBI NIH HHS HL106184NHLBI NIH HHS R01 HL106184NIDDK NIH HHS DK072442NIDDK NIH HHS DK086267NIDDK NIH HHS P30 DK072442NIDDK NIH HHS R01 DK086267
6 · The paper itself

Abstract

Serum response factor and its transcriptional cofactor MKL1 are critical for megakaryocyte maturation and platelet formation. We show that MKL2, a homologue of MKL1, is expressed in megakaryocytes and plays a role in megakaryocyte maturation. Using a megakaryocyte-specific Mkl2 knockout (KO) mouse on the conventional Mkl1 KO background to produce double KO (DKO) megakaryocytes and platelets, a critical role for MKL2 is revealed. The decrease in megakaryocyte ploidy and platelet counts of DKO mice is more severe than in Mkl1 KO mice. Platelet dysfunction in DKO mice is revealed by prolonged bleeding times and ineffective platelet activation in vitro in response to adenosine 5'-diphosphate. Electron microscopy and immunofluorescence of DKO megakaryocytes and platelets indicate abnormal cytoskeletal and membrane organization with decreased granule complexity. Surprisingly, the DKO mice have a more extreme thrombocytopenia than mice lacking serum response factor (SRF) expression in the megakaryocyte compartment. Comparison of gene expression reveals approximately 4400 genes whose expression is differentially affected in DKO compared with megakaryocytes deficient in SRF, strongly suggesting that MKL1 and MKL2 have both SRF-dependent and SRF-independent activity in megakaryocytopoiesis.

Indexed as

HematopoiesisAdenosine DiphosphateAnimalsBleeding TimeBlood PlateletsBone Marrow CellsCells, CulturedCrosses, GeneticCytoplasmCytoskeletonGene Expression ProfilingMegakaryocytesMiceMice, Inbred C57BLMice, KnockoutOligonucleotide Array Sequence AnalysisAdenosine DiphosphateMrtfa protein, mouseMRTFB protein, humanTrans-ActivatorsTranscription Factors

Identifiers

PMID22806889
PMCPMC3447785
OpenAlexW2056153432

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.