Evidence map›Paper›PMID 38335962›Full record

ArticleStem cell reports2024

ER stress and lipid imbalance drive diabetic embryonic cardiomyopathy in an organoid model of human heart development.

Aleksandra Kostina, Yonatan R Lewis-Israeli, Mishref Abdelhamid, Mitchell A Gabalski, Artem Kiselev, Brett D Volmert, Haley Lankerd, Amanda R Huang, Aaron H Wasserman, Todd Lydic and 4 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
10.9field-weighted citation impact, top 1% 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

19 citing papers in PubMed, 22 citations in OpenAlex.

  1. Article
  2. Human cardiovascular organoids: Biomedical applications and ethical challenges.American heart journal plus : cardiology research and practice · 2026
    Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Review
  19. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 1 institution in 1 country.

Aleksandra KostinaDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA.
Yonatan R Lewis-IsraeliDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA.
Mishref AbdelhamidDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
Mitchell A GabalskiDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA.
Artem KiselevDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, MI, USA; Division of Dermatology, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA.
Brett D VolmertDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA.
Haley LankerdDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA.
Amanda R HuangDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA.
Aaron H WassermanDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA.
Todd LydicDepartment of Physiology, Michigan State University, MI, USA.
Christina ChanDepartment of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA; Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA; Division of Biomedical Devices, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
Sangbum ParkDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, College of Human Medicine, Michigan State University, MI, USA; Division of Dermatology, Department of Medicine, College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA.
Isoken OlomuDivision of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
Aitor AguirreDivision of Developmental and Stem Cell Biology, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA; Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI, USA. Electronic address: aaguirre@msu.edu.
Michigan State University · US

Funding

Oxylipin Signaling in Congenital Heart DiseaseR01HL151505 · NHLBI · MICHIGAN STATE UNIVERSITY · PI AGUIRRE, AITOR · 2021 to 2025
$2.2M
Lipid signaling in cardiac development and diseaseK01HL135464 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI AGUIRRE, AITOR · 2017 to 2021
$795k
NHLBI NIH HHS K01 HL135464NHLBI NIH HHS R01 HL151505
6 · The paper itself

Abstract

Congenital heart defects are the most prevalent human birth defects, and their incidence is exacerbated by maternal health conditions, such as diabetes during the first trimester (pregestational diabetes). Our understanding of the pathology of these disorders is hindered by a lack of human models and the inaccessibility of embryonic tissue. Using an advanced human heart organoid system, we simulated embryonic heart development under pregestational diabetes-like conditions. These organoids developed pathophysiological features observed in mouse and human studies before, including ROS-mediated stress and cardiomyocyte hypertrophy. scRNA-seq revealed cardiac cell-type-specific dysfunction affecting epicardial and cardiomyocyte populations and alterations in the endoplasmic reticulum and very-long-chain fatty acid lipid metabolism. Imaging and lipidomics confirmed these findings and showed that dyslipidemia was linked to fatty acid desaturase 2 mRNA decay dependent on IRE1-RIDD signaling. Targeting IRE1 or restoring lipid levels partially reversed the effects of pregestational diabetes, offering potential preventive and therapeutic strategies in humans.

Indexed as

CardiomyopathiesDiabetes MellitusHeart Defects, CongenitalAnimalsEndoplasmic Reticulum StressHumansLipidsMiceOrganoidsProtein Serine-Threonine KinasesLipidsProtein Serine-Threonine Kinasescongenital heart defectsheart developmentheart organoidomega-3 fatty acidpluripotent stem cellpregestational diabetesvery-long-chain fatty acid

Identifiers

PMID38335962
PMCPMC10937107
OpenAlexW4391643805

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.