Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes

Abstract Microtia is a congenital malformation characterized by underdevelopment of the external ear. While chondrocyte dysfunction has been implicated in microtia, the specific cellular abnormalities remain poorly understood. This study aimed to investigate mitochondrial dysfunction in microtia cho...

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Main Authors: Xinyu Li, Datao Li, Ruhong Zhang
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-025-85169-x
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author Xinyu Li
Datao Li
Ruhong Zhang
author_facet Xinyu Li
Datao Li
Ruhong Zhang
author_sort Xinyu Li
collection DOAJ
description Abstract Microtia is a congenital malformation characterized by underdevelopment of the external ear. While chondrocyte dysfunction has been implicated in microtia, the specific cellular abnormalities remain poorly understood. This study aimed to investigate mitochondrial dysfunction in microtia chondrocytes using single-cell RNA sequencing. Cartilage samples were obtained from patients with unilateral, non-syndromic microtia and healthy controls. Single-cell RNA sequencing was performed using the 10 × Genomics platform. Bioinformatic analyses including cell type identification, trajectory analysis, and gene co-expression network analysis were conducted. Mitochondrial function was assessed through ROS levels, membrane potential, and transmission electron microscopy. Chondrocytes from microtia samples showed lower mitochondrial function scores compared to normal samples. Trajectory analysis revealed more disorganized differentiation patterns in microtia chondrocytes. Mitochondrial dysfunction in microtia chondrocytes was confirmed by increased ROS production, decreased membrane potential, and altered mitochondrial structure. Gene co-expression network analysis identified hub genes associated with mitochondrial function, including SDHA, SIRT1, and PGC1A, which showed reduced expression in microtia chondrocytes. This study provides evidence of mitochondrial dysfunction in microtia chondrocytes and identifies potential key genes involved in this process. These findings offer new insights into the pathogenesis of microtia and may guide future therapeutic strategies.
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spelling doaj-art-e44babaf16e44b4e8a89883c027e74032025-08-20T02:59:32ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-85169-xSingle-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytesXinyu Li0Datao Li1Ruhong Zhang2Department of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Plastic and Reconstructive Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineAbstract Microtia is a congenital malformation characterized by underdevelopment of the external ear. While chondrocyte dysfunction has been implicated in microtia, the specific cellular abnormalities remain poorly understood. This study aimed to investigate mitochondrial dysfunction in microtia chondrocytes using single-cell RNA sequencing. Cartilage samples were obtained from patients with unilateral, non-syndromic microtia and healthy controls. Single-cell RNA sequencing was performed using the 10 × Genomics platform. Bioinformatic analyses including cell type identification, trajectory analysis, and gene co-expression network analysis were conducted. Mitochondrial function was assessed through ROS levels, membrane potential, and transmission electron microscopy. Chondrocytes from microtia samples showed lower mitochondrial function scores compared to normal samples. Trajectory analysis revealed more disorganized differentiation patterns in microtia chondrocytes. Mitochondrial dysfunction in microtia chondrocytes was confirmed by increased ROS production, decreased membrane potential, and altered mitochondrial structure. Gene co-expression network analysis identified hub genes associated with mitochondrial function, including SDHA, SIRT1, and PGC1A, which showed reduced expression in microtia chondrocytes. This study provides evidence of mitochondrial dysfunction in microtia chondrocytes and identifies potential key genes involved in this process. These findings offer new insights into the pathogenesis of microtia and may guide future therapeutic strategies.https://doi.org/10.1038/s41598-025-85169-xMicrotiaChondrocytesMitochondrial dysfunctionSingle-cell sequencing
spellingShingle Xinyu Li
Datao Li
Ruhong Zhang
Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes
Scientific Reports
Microtia
Chondrocytes
Mitochondrial dysfunction
Single-cell sequencing
title Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes
title_full Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes
title_fullStr Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes
title_full_unstemmed Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes
title_short Single-Cell RNA sequencing reveals mitochondrial dysfunction in microtia chondrocytes
title_sort single cell rna sequencing reveals mitochondrial dysfunction in microtia chondrocytes
topic Microtia
Chondrocytes
Mitochondrial dysfunction
Single-cell sequencing
url https://doi.org/10.1038/s41598-025-85169-x
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AT dataoli singlecellrnasequencingrevealsmitochondrialdysfunctioninmicrotiachondrocytes
AT ruhongzhang singlecellrnasequencingrevealsmitochondrialdysfunctioninmicrotiachondrocytes