Selenium promotes neural development through the regulation of GPX4 and SEPP1 in an iPSC-derived neuronal model

Zhenzhu Dai; Yanzi Yu; Ruhai Chen; Hongyao Zhu; Hin Fong; Junxin Kuang; Yunbo Jiang; Yalan Chen; Yimei Niu; Tianfeng Chen; Lingling Shi

doi:10.1016/j.biomaterials.2024.123011

Selenium promotes neural development through the regulation of GPX4 and SEPP1 in an iPSC-derived neuronal model

Biomaterials. 2024 Dec 15:316:123011. doi: 10.1016/j.biomaterials.2024.123011. Online ahead of print.

Authors

Zhenzhu Dai¹, Yanzi Yu¹, Ruhai Chen¹, Hongyao Zhu¹, Hin Fong², Junxin Kuang³, Yunbo Jiang¹, Yalan Chen¹, Yimei Niu¹, Tianfeng Chen⁴, Lingling Shi⁵

Affiliations

¹ State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-Human Primate Research, GHM Institute of CNS Regeneration, Department of Chemistry, Jinan University, Guangzhou, 510632, China.
² Faculty of Medicine, International School, Jinan University, Guangzhou, 510632, China.
³ Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
⁴ State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-Human Primate Research, GHM Institute of CNS Regeneration, Department of Chemistry, Jinan University, Guangzhou, 510632, China; Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China. Electronic address: tchentf@jnu.edu.cn.
⁵ State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong Key Laboratory of Non-Human Primate Research, GHM Institute of CNS Regeneration, Department of Chemistry, Jinan University, Guangzhou, 510632, China; Department of Psychiatry, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China; Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, 226019, China; Department of Neurology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570100, China. Electronic address: tlingshi@jnu.edu.cn.

PMID: 39708777
DOI: 10.1016/j.biomaterials.2024.123011

Abstract

Selenium (Se) is incorporated into selenoproteins in the form of selenocysteine, which has biological functions associated with neural development. Unfortunately, the specific roles and mechanisms of selenoproteins at different stages of neuronal development are still unclear. Therefore, in this study, we successfully established a neuronal model derived from induced pluripotent stem cells (iPSC-iNeuron) and used Se nanoparticles (SeNPs@LNT) with high bioavailability to intervene at different stages of neural development in iPSC-iNeuron model. Interestingly, our results showed that SeNPs@LNT could not only accelerate the proliferation of neural progenitor cells (NPCs) by upregulating glutathione peroxidase 4 (GPX4) during the NPC stage, but also can promote neuronal differentiation by increasing selenoprotein P (SEPP1) during the neuronal stage, resulting in efficient and rapid neural development. In addition, further mechanistic studies showed that SeNPs@LNT can regulate selenoproteins by activating the PI3K/Akt/Nrf2 signaling pathway, thereby affecting neuronal development. Notably, Further analysis of ASD patients in National Center for Biotechnology Information single-cell RNA-seq datasets also revealed significantly lower GPX4 expression within NRGN-expressing neurons in ASD patients, and GO enrichment analysis of genes in NRGN-expressing neurons from ASD patients showed that the downregulation of selenoproteins due to aberrant selenoprotein synthesis may be closely associated with decreased ATP synthesis resulting from abnormal mitochondrial and respiratory chain signaling pathways. Taken together, this study provides evidence that SeNPs@LNT exerts a beneficial effect on early neural development through the regulation of selenoproteins.

Keywords: Neural development; SeNPs@LNT; Selenoproteins; iPSC-iNeuron model.