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ER stress and lipid imbalance drive diabetic embryonic cardiomyopathy in an organoid model of human heart development.
Kostina, Aleksandra; Lewis-Israeli, Yonatan R; Abdelhamid, Mishref; Gabalski, Mitchell A; Kiselev, Artem; Volmert, Brett D; Lankerd, Haley; Huang, Amanda R; Wasserman, Aaron H; Lydic, Todd; Chan, Christina; Park, Sangbum; Olomu, Isoken; Aguirre, Aitor.
Afiliación
  • Kostina A; Division 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.
  • Lewis-Israeli YR; Division 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.
  • Abdelhamid M; Division 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, M
  • Gabalski MA; Division 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.
  • Kiselev A; Division 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
  • Volmert BD; Division 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.
  • Lankerd H; Division 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.
  • Huang AR; Division 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.
  • Wasserman AH; Division 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.
  • Lydic T; Department of Physiology, Michigan State University, MI, USA.
  • Chan C; Department 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 En
  • Park S; Division 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
  • Olomu I; Division of Neonatology, Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, East Lansing, MI, USA.
  • Aguirre A; Division 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@m
Stem Cell Reports ; 19(3): 317-330, 2024 Mar 12.
Article en En | MEDLINE | ID: mdl-38335962
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus / Cardiopatías Congénitas / Cardiomiopatías Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Stem Cell Reports Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Diabetes Mellitus / Cardiopatías Congénitas / Cardiomiopatías Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Stem Cell Reports Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos