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ORIGINAL RESEARCH article

Front. Genet.
Sec. Neurogenomics
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1483574

Unveiling the Role of IGF1R in Autism Spectrum Disorder: A Multi-Omics Approach to Decipher Common Pathogenic Mechanisms in the IGF Signaling Pathway

Provisionally accepted
Kang Yang Kang Yang 1Tian Zhang Tian Zhang 2Ruize Niu Ruize Niu 3Liyang Zhao Liyang Zhao 1Zhonghe Cheng Zhonghe Cheng 1Jun Li Jun Li 1*Lifang Wang Lifang Wang 1*
  • 1 National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, Beijing Municipality, China
  • 2 Affiliated Mental Health Center & Hangzhou Seventh People's Hospital and School of Brain Science and Brain Medicine, Zhejiang University School of Medicine,, Hangzhou, China
  • 3 Affiliated Mental Health Center of Kuming medicine University, kunming, China

The final, formatted version of the article will be published soon.

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention.

    Keywords: Autism Spectrum Disorder, IGF signaling pathway, multi-omics, IGF1R, Neurodevelopmental mechanisms

    Received: 20 Aug 2024; Accepted: 09 Sep 2024.

    Copyright: © 2024 Yang, Zhang, Niu, Zhao, Cheng, Li and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jun Li, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, 100191, Beijing Municipality, China
    Lifang Wang, National Clinical Research Center for Mental Disorders, Peking University Sixth Hospital, Beijing, 100191, Beijing Municipality, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.