Gene regulation analysis of patient-derived iPSCs and its CRISPR-corrected control provides a new tool for studying perturbations of ELMOD3 c.512A>G mutation during the development of inherited hearing loss

Xianlin Liu; Jie Wen; Xuezhong Liu; Anhai Chen; Sijun Li; Jing Liu; Jie Sun; Wei Gong; Xiaoming Kang; Zhili Feng; Chufeng He; Lingyun Mei; Jie Ling; Yong Feng

doi:10.1371/journal.pone.0288640

Gene regulation analysis of patient-derived iPSCs and its CRISPR-corrected control provides a new tool for studying perturbations of ELMOD3 c.512A>G mutation during the development of inherited hearing loss

PLoS One. 2023 Sep 14;18(9):e0288640. doi: 10.1371/journal.pone.0288640. eCollection 2023.

Authors

Xianlin Liu^{1

2}, Jie Wen^{3

4}, Xuezhong Liu⁵, Anhai Chen^{1

2}, Sijun Li^{1

2}, Jing Liu^{1

2}, Jie Sun⁶, Wei Gong^{3

4}, Xiaoming Kang^{3

4}, Zhili Feng^{3

4}, Chufeng He^{1

2}, Lingyun Mei^{1

2}, Jie Ling⁷, Yong Feng^{1

3

4}

Affiliations

¹ Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² Key Laboratory of Otolaryngology Major Disease Research of Hunan Province, Changsha, Hunan, China.
³ Department of Otolaryngology Head and Neck Surgery, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China.
⁴ Institute of Otolaryngology Head and Neck Surgery, University of South China, Changsha, Hunan, China.
⁵ Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, FL, United States of America.
⁶ Department of Otolaryngology Head and Neck Surgery, The Eighth Affiliated Hospital, Sun Yat-sen University, Futian District, Shenzhen, China.
⁷ Medical Functional Experiment Center, School of Basic Medical Science, Central South University, Changsha, Hunan, China.

Abstract

The ELMOD3 gene is implicated in causing autosomal recessive/dominant non-syndromic hearing loss in humans. However, the etiology has yet to be completely elucidated. In this study, we generated a patient-derived iPSC line carrying ELMOD3 c.512A>G mutation. In addition, the patient-derived iPSC line was corrected by CRISPR/Cas9 genome editing system. Then we applied RNA sequencing profiling to compare the patient-derived iPSC line with different controls, respectively (the healthy sibling-derived iPSCs and the CRISPR/Cas9 corrected iPSCs). Functional enrichment and PPI network analysis revealed that differentially expressed genes (DEGs) were enriched in the gene ontology, such as sensory epithelial development, intermediate filament cytoskeleton organization, and the regulation of ion transmembrane transport. Our current work provided a new tool for studying how disruption of ELMOD3 mechanistically drives hearing loss.

Copyright: © 2023 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Deafness*
GTPase-Activating Proteins
Gene Expression Regulation
Hearing Loss* / genetics
Humans
Induced Pluripotent Stem Cells*
Mutation

Substances

ELMOD3 protein, human
GTPase-Activating Proteins

Grants and funding

This work was supported by the National Key Research and Development Program of China [Grant No. 2020YFC2005204] awarded to YF; the National Natural Science Foundation of China [Grant No. 82101233, 82271187 and 82071065]; the Startup Project from the University of South China [Grant No. 201RGC002]; the University of South China Clinical Research 4310 Program; the Fundamental Research Funds for the Central Universities of Central South University [Grant No. 1053320190364]; the Natural Science Foundation of Hunan Province [Grant No. 2022JJ30506]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.