Evidence map›Paper›PMID 27924221›Full record

ArticleCell discovery2016

Targeting Mll1 H3K4 methyltransferase activity to guide cardiac lineage specific reprogramming of fibroblasts.

Liu Liu, Ienglam Lei, Hacer Karatas, Yangbing Li, Li Wang, Leonid Gnatovskiy, Yali Dou, Shaomeng Wang, Li Qian, Zhong Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell discovery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
–field-weighted citation impact
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

30 citing papers in PubMed.

  1. Review
  2. Advances in fibroblast-based cardiac reprogramming in the treatment of heart disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. High Yap and Mll1 promote a persistent regenerative cell state induced by Notch signaling and loss of p53.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  15. Article
  16. Review
  17. In Vitro Conversion of Murine Fibroblasts into Cardiomyocyte-Like Cells.Methods in molecular biology (Clifton, N.J.) · 2021
    Article
  18. Article
  19. Review
  20. Review
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

10 authors.

Liu LiuDepartment of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan , Ann Arbor, MI, USA.
Ienglam LeiDepartment of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan, Ann Arbor, MI, USA; Faculty of Health Sciences, University of Macau, Macau SAR, China.
Hacer KaratasDepartment of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Medicinal Chemistry, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Yangbing LiDepartment of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Medicinal Chemistry, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Li WangDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA; McAllister Heart Institute University of North Carolina, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Leonid GnatovskiyDepartment of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan , Ann Arbor, MI, USA.
Yali DouDepartment of Pathology, University of Michigan Medical School, 1301 Catherine , Ann Arbor, MI, USA.
Shaomeng WangDepartment of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, MI, USA; Department of Medicinal Chemistry, University of Michigan College of Pharmacy, Ann Arbor, MI, USA.
Li QianDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA; McAllister Heart Institute University of North Carolina, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
Zhong WangDepartment of Cardiac Surgery, Frankel Cardiovascular Center, The University of Michigan , Ann Arbor, MI, USA.

Funding

Molecular mechanisms of direct cardiac reprogrammingR01HL128331 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI QIAN, LI · 2016 to 2020
$2.1M
Epigenetic control of multipotent cardiac progenitor cell differentiationR01HL109054 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI WANG, ZHONG · 2012 to 2016
$1.9M
Targeting the MLL-WDR5 protein-protein interactionR01CA177307 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI DOU, YALI, WANG, SHAOMENG · 2013 to 2016
$1.8M
NCI NIH HHS R01 CA177307NHLBI NIH HHS R01 HL109054NHLBI NIH HHS R01 HL128331
6 · The paper itself

Abstract

Generation of induced cardiomyocytes (iCMs) directly from fibroblasts offers a great opportunity for cardiac disease modeling and cardiac regeneration. A major challenge of iCM generation is the low conversion rate. To address this issue, we attempted to identify small molecules that could potentiate the reprogramming ability towards cardiac fate by removing inhibitory roadblocks. Using mouse embryonic fibroblasts as the starting cell source, we first screened 47 cardiac development related epigenetic and transcription factors, and identified an unexpected role of H3K4 methyltransferase Mll1 and related factor Men1 in inhibiting iCM reprogramming. We then applied small molecules (MM408 and MI503) of Mll1 pathway inhibitors and observed an improved efficiency in converting embryonic fibroblasts and cardiac fibroblasts into functional cardiomyocyte-like cells. We further observed that these inhibitors directly suppressed the expression of Mll1 target gene

Indexed as

adipocyteCardiac reprogrammingcardiomyocyteH3K4 methyltransferaseMll1 inhibitor

Identifiers

PMID27924221
PMCPMC5113048

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.