Zeng SX, Ye JT, Huang SH, Liu RX. X inactive-specific transcript regulates mitochondrial function and neuronal differentiation of stem cells via IGF2BP2/CPT1A axis in models of spinal cord injury. World J Stem Cells 2025; 17(7): 101929 [PMID: 40740537 DOI: 10.4252/wjsc.v17.i7.101929]
Corresponding Author of This Article
Si-Hua Huang, MD, Associate Chief Physician, Department of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an 710004, Shaanxi Province, China. mbyp180@163.com
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Cell & Tissue Engineering
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Basic Study
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Zeng SX, Ye JT, Huang SH, Liu RX. X inactive-specific transcript regulates mitochondrial function and neuronal differentiation of stem cells via IGF2BP2/CPT1A axis in models of spinal cord injury. World J Stem Cells 2025; 17(7): 101929 [PMID: 40740537 DOI: 10.4252/wjsc.v17.i7.101929]
World J Stem Cells. Jul 26, 2025; 17(7): 101929 Published online Jul 26, 2025. doi: 10.4252/wjsc.v17.i7.101929
X inactive-specific transcript regulates mitochondrial function and neuronal differentiation of stem cells via IGF2BP2/CPT1A axis in models of spinal cord injury
Si-Xiang Zeng, Jin-Tao Ye, Si-Hua Huang, Ruo-Xi Liu
Si-Xiang Zeng, Jin-Tao Ye, Si-Hua Huang, Ruo-Xi Liu, Department of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, Xi’an 710004, Shaanxi Province, China
Co-corresponding authors: Si-Hua Huang and Ruo-Xi Liu.
Author contributions: Huang SH was the guarantor and designed the study; Zeng SX and Ye JT participated in the acquisition, analysis, and interpretation of the data and drafted the initial manuscript; Ye JT, Huang SH, and Liu RX revised the article critically for important intellectual content; All authors participated in this study and jointly reviewed and edited the manuscript. Huang SH and Liu RX as corresponding authors have made equal contributions to this work. There are three main reasons for deciding to designate Huang SH and Liu RX as co-corresponding authors. First, this study was conducted as a collaborative effort, and it is reasonable to designate a co-corresponding author. The author accurately reflects the allocation of responsibilities and burdens related to the time and effort required to complete the research and final manuscript. Designating two co-corresponding authors will ensure effective communication and management of post submission matters, thereby improving the quality and reliability of the paper. Second, the co-corresponding authors of the research team come from the same field of expertise and skills, and their appointments best reflect this diversity. It also promotes the most comprehensive and in-depth exploration of research topics, ultimately enriching readers’ understanding by providing various expert perspectives. Third, throughout the entire research process, Huang SH and Liu RX contributed equallly. These researchers were selected as co-corresponding authors, acknowledging and respecting their equal contributions, demonstrating the spirit of collaboration and teamwork in this study. We believe that designating Huang SH and Liu RX as co-corresponding authors is suitable for our manuscript as it accurately reflects our team’s spirit of cooperation, equal contribution, and diversity.
Institutional animal care and use committee statement: All procedures involving animals are reviewed and approved by the Institutional Animal Care and Use Committee of the Second Affiliated Hospital of Xi’an Jiaotong University, No. JW-WW-2022091107.
Conflict-of-interest statement: All authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The original contributions presented in the study are included in the article. Further inquiries can be directed to the corresponding authors.
Corresponding author: Si-Hua Huang, MD, Associate Chief Physician, Department of Orthopaedic Surgery, Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an 710004, Shaanxi Province, China. mbyp180@163.com
Received: February 12, 2025 Revised: March 7, 2025 Accepted: June 25, 2025 Published online: July 26, 2025 Processing time: 162 Days and 1.3 Hours
Abstract
BACKGROUND
Spinal cord injury (SCI) often results in irreversible neurological deficits; therefore, effective treatment is urgently needed. Neural stem cells (NSCs) have excellent differentiation potential. However, the role of the long noncoding RNA X inactive-specific transcript (XIST) in NSCs and SCI remains unclear.
AIM
To explore the role of XIST in enhancing NSC function and its therapeutic potential in SCI.
METHODS
We used in vitro and in vivo models to examine the effects of XIST on NSCs. XIST was overexpressed in NSCs, and its impact on mitochondrial function, neuronal differentiation, and the insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2)/carnitine palmitoyl transferase 1A (CPT1A) pathway was assessed using a series of biochemical assays, quantitative PCR, and Seahorse XF24 analysis. A mouse model of SCI was used to evaluate the therapeutic effects of XIST in vivo.
RESULTS
Overexpression of XIST in NSCs significantly increased mitochondrial membrane potential, ATP production, and oxygen consumption rate. XIST also promoted NSC proliferation and neuronal differentiation while inhibiting astrocytic differentiation. Mechanistically, XIST regulated CPT1A expression post-transcriptionally by interacting with IGF2BP2. In vivo XIST-treated mice exhibited improved motor scores and reduced proinflammatory cytokine expression following SCI.
CONCLUSION
These findings suggested that XIST modulated mitochondrial function and neural differentiation in NSCs through the IGF2BP2/CPT1A pathway. While preliminary in vivo results are encouraging, further studies are needed to determine the long-term therapeutic relevance and underlying mechanisms of XIST in SCI recovery.
Core Tip: This study highlighted the critical role of long non-coding RNA X inactive-specific transcript (XIST) in enhancing neural stem cell function for spinal cord injury (SCI) treatment. XIST significantly improved motor recovery and reduced inflammation in mouse models of SCI by promoting mitochondrial function and neuronal differentiation. These findings suggested that XIST regulated carnitine palmitoyl transferase 1A expression via the insulin-like growth factor 2 mRNA binding protein 2 pathway, providing a promising therapeutic target for the development of effective interventions against irreversible neurological deficits in SCI. Further exploration of the long-term effects of XIST may advance its clinical applications.
