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Single cell regulatory architecture of human pancreatic islets suggests sex differences in ß cell function and the pathogenesis of type 2 diabetes.
Qadir, Mirza Muhammad Fahd; Elgamal, Ruth M; Song, Keijing; Kudtarkar, Parul; Sakamuri, Siva S V P; Katakam, Prasad V; El-Dahr, Samir S; Kolls, Jay K; Gaulton, Kyle J; Mauvais-Jarvis, Franck.
Afiliación
  • Qadir MMF; Section of Endocrinology and Metabolism, John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
  • Elgamal RM; Southeast Louisiana Veterans Health Care System, New Orleans, LA, USA.
  • Song K; Tulane Center of Excellence in Sex-Based Biology & Medicine, New Orleans, LA, USA.
  • Kudtarkar P; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA.
  • Sakamuri SSVP; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
  • Katakam PV; Center for Translational Research in Infection and Inflammation, John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
  • El-Dahr SS; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
  • Kolls JK; Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
  • Gaulton KJ; Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA, USA.
  • Mauvais-Jarvis F; Department of Pediatrics, Tulane University, School of Medicine, New Orleans, LA, USA.
Res Sq ; 2024 Jul 03.
Article en En | MEDLINE | ID: mdl-39011095
ABSTRACT
Type 2 and type 1 diabetes (T2D, T1D) exhibit sex differences in insulin secretion, the mechanisms of which are unknown. We examined sex differences in human pancreatic islets from 52 donors with and without T2D combining single cell RNA-seq (scRNA-seq), single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), hormone secretion, and bioenergetics. In nondiabetic (ND) donors, sex differences in islet cells gene accessibility and expression predominantly involved sex chromosomes. Islets from T2D donors exhibited similar sex differences in sex chromosomes differentially expressed genes (DEGs), but also exhibited sex differences in autosomal genes. Comparing ß cells from T2D vs. ND donors, gene enrichment of female ß cells showed suppression in mitochondrial respiration, while male ß cells exhibited suppressed insulin secretion. Thus, although sex differences in gene accessibility and expression of ND ß cells predominantly affect sex chromosomes, the transition to T2D reveals sex differences in autosomes highlighting mitochondrial failure in females.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Res Sq Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos