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ARTICLE TYPE : RESEARCH ARTICLE

Published on :   15 Dec 2025, Volume - 1
Journal Title :   WebLog Journal of Stem Cells Research and Therapy | WebLog J Stem Cell Res Ther
Source URL:   weblog iconhttps://weblogoa.com/articles/wjscrt.2025.l1501
Permanent Identifier (DOI) :  doi iconhttps://doi.org/10.5281/zenodo.18001084

Microarray Analysis of VHL-gene-transferred Neural Stem Cells Around Transcriptional Signaling Pathways of Neuronal Differentiation

Kimihiro Nakahara 1
Akira Saito 1
Akira Matsuno 1
Atsuhiko Kubo 2,3
Hidetoshi Murata 4
Hiroshi Kanno 2,4 *
1Department of Neurosurgery, International University of Health and Welfare, Narita, Japan
2Department of Neurosurgery, Yokohama City University, Yokohama, Japan
3Nerve Care Clinic, Yokosuka, Japan
4Department of Neurosurgery, St. Marianna University School of Medicine, Kawasaki, Japan

Abstract

Previously, we reported that the von Hippel-Lindau (VHL) tumor suppressor gene induces neural stem cell (NSC) differentiation to neurons, and that VHL's involvement in differentiating NSCs or mesenchymal stem cells (MSCs) into neurons is related to the inhibition of the JAK/STAT pathway through the proteasomal degradation of proteins following their ubiquitination by the VHL/ elonginBC/Cul2 complex. However, the relationship between VHL and other pathways and factors around VHL-mediated neuronal differentiation is still unclear. In this study, the VHL gene was transferred to adult rat NSCs, and the gene expression profiles of the VHL-gene-transferred and control NSCs were analyzed using cDNA arrays. Then, the genes of the transcriptional signaling pathways around the VHL gene were examined. In particular, we examined the expression profiles of VHL-downstream genes, neurogenesis genes, hormonal genes, cytokine genes, and ubiquitin/ proteasome genes. VHL-transfected NSCs showed increased expression of most neurochemical and neurogenesis genes, hormonal genes, homeobox genes, and cytokine genes. However, they showed decreased expression of VHL-downstream genes (HIF/VEGF/EPO, JAK/STAT/Smad), neurogenesis-associated genes (Wnt, Notch, and GFAP), and ubiquitin/proteasome genes. Meanwhile, the expression of neurotrophic factors was either increased or decreased. cDNA microarray analysis revealed that VHL not only regulates neuronal differentiation and the HIF/ VEGF/EPO and JAK/STAT/Smad pathways but also development, hormones, and cytokines. Understanding the transcriptional signaling pathways around VHL that induce neuronal differentiation is very important in neuronal regenerative medicine.

Keywords: cDNA Microarray; VHL; Neural Stem Cells; Neuronal Differentiation; Transcriptional Signaling Pathway

Citation

Nakahara K, Saito A, Matsuno A, Kubo A, Murata H, Kanno H. Microarray Analysis of VHL-gene transferred Neural Stem Cells Around Transcriptional Signaling Pathways of Neuronal Differentiation. WebLog J Stem Cell Res Ther. wjscrt.2025.l1501. https://doi.org/10.5281/zenodo.18001084
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