Evidence map›Paper›PMID 37429859›Full record

ArticleNature communications2023

Engineered MED12 mutations drive leiomyoma-like transcriptional and metabolic programs by altering the 3D genome compartmentalization.

Kadir Buyukcelebi, Xintong Chen, Fatih Abdula, Hoda Elkafas, Alexander James Duval, Harun Ozturk, Fidan Seker-Polat, Qiushi Jin, Ping Yin, Yue Feng and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
6.2field-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

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. UTERINE FIBROIDS.Physiological reviews · 2025
    Review
  10. MED12 dysregulation: insights into cancer and therapeutic resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Kadir BuyukcelebiRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0009-0009-4653-7931
Xintong ChenDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine Northwestern University, Chicago, IL, USA.
Fatih AbdulaRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-2728-5160
Hoda ElkafasRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-1058-3399
Alexander James DuvalRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.
Harun OzturkRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.
Fidan Seker-PolatRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.
Qiushi JinDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine Northwestern University, Chicago, IL, USA.
Ping YinRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.
Yue FengDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Serdar E BulunRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.
Jian Jun WeiRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0003-0281-2793
Feng YueDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine Northwestern University, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-7954-5462
Mazhar AdliRobert Lurie Comprehensive Cancer Center, Department of Obstetrics and Gynecology, Feinberg School of Medicine at Northwestern University, Chicago, IL, USA. adli@northwestern.edu.ORCID http://orcid.org/0000-0003-4740-9594
Northwestern University · US

Funding

The Origin and Cellular Heterogeneity of Uterine LeiomyomasP50HD098580 · NICHD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BULUN, SERDAR E. · 2019 to 2023
$7.4M
NICHD NIH HHS P50 HD098580
6 · The paper itself

Abstract

Nearly 70% of Uterine fibroid (UF) tumors are driven by recurrent MED12 hotspot mutations. Unfortunately, no cellular models could be generated because the mutant cells have lower fitness in 2D culture conditions. To address this, we employ CRISPR to precisely engineer MED12 Gly44 mutations in UF-relevant myometrial smooth muscle cells. The engineered mutant cells recapitulate several UF-like cellular, transcriptional, and metabolic alterations, including altered Tryptophan/kynurenine metabolism. The aberrant gene expression program in the mutant cells is, in part, driven by a substantial 3D genome compartmentalization switch. At the cellular level, the mutant cells gain enhanced proliferation rates in 3D spheres and form larger lesions in vivo with elevated production of collagen and extracellular matrix deposition. These findings indicate that the engineered cellular model faithfully models key features of UF tumors and provides a platform for the broader scientific community to characterize genomics of recurrent MED12 mutations.

Indexed as

LeiomyomaClustered Regularly Interspaced Short Palindromic RepeatsGenomicsHumansMediator ComplexMutationMyocytes, Smooth MuscleTranscription FactorsMED12 protein, humanMediator ComplexTranscription Factors

Identifiers

PMID37429859
PMCPMC10333368
OpenAlexW4383695462

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.