Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain

Naoya Murao, Shuzo Matsubara, Taito Matsuda, Hirofumi Noguchi, Tetsuji Mutoh, Masahiro Mutoh, Haruhiko Koseki, Masakazu Namihira, Kinichi Nakashima

Research output: Contribution to journalArticle

Abstract

Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis. Specific ablation of Np95 in adult NS/PCs (aNS/PCs) led to a decrease in their proliferation and an impairment of neuronal differentiation and to suppression of neuronal maturation associated with the impairment of dendritic formation in the hippocampal DG. We also found that deficiency of Np95 in NS/PCs increased the expression of tumor suppressor genes p16 and p53, and confirmed that expression of these genes in NS/PCs recapitulates the phenotype of Np95-deficient NS/PCs. Taken together, our findings suggest that Np95 plays an essential role in proliferation and differentiation of aNS/PCs through the regulation of tumor suppressor gene expression in adult neurogenesis.

Original languageEnglish
Pages (from-to)31-43
Number of pages13
JournalNeuroscience Research
Volume143
DOIs
Publication statusPublished - Jun 1 2019

Fingerprint

Neural Stem Cells
Neurogenesis
Tumor Suppressor Genes
Gene Expression
Brain
Parahippocampal Gyrus
Dentate Gyrus
Adult Stem Cells
Lateral Ventricles
DNA Methylation
Nuclear Proteins
Cell Division
Brain Injuries
Learning
Phenotype
Neurons
Proteins

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain. / Murao, Naoya; Matsubara, Shuzo; Matsuda, Taito; Noguchi, Hirofumi; Mutoh, Tetsuji; Mutoh, Masahiro; Koseki, Haruhiko; Namihira, Masakazu; Nakashima, Kinichi.

In: Neuroscience Research, Vol. 143, 01.06.2019, p. 31-43.

Research output: Contribution to journalArticle

Murao, Naoya ; Matsubara, Shuzo ; Matsuda, Taito ; Noguchi, Hirofumi ; Mutoh, Tetsuji ; Mutoh, Masahiro ; Koseki, Haruhiko ; Namihira, Masakazu ; Nakashima, Kinichi. / Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain. In: Neuroscience Research. 2019 ; Vol. 143. pp. 31-43.
@article{70d726a388b54469b58801eee473be51,
title = "Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain",
abstract = "Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis. Specific ablation of Np95 in adult NS/PCs (aNS/PCs) led to a decrease in their proliferation and an impairment of neuronal differentiation and to suppression of neuronal maturation associated with the impairment of dendritic formation in the hippocampal DG. We also found that deficiency of Np95 in NS/PCs increased the expression of tumor suppressor genes p16 and p53, and confirmed that expression of these genes in NS/PCs recapitulates the phenotype of Np95-deficient NS/PCs. Taken together, our findings suggest that Np95 plays an essential role in proliferation and differentiation of aNS/PCs through the regulation of tumor suppressor gene expression in adult neurogenesis.",
author = "Naoya Murao and Shuzo Matsubara and Taito Matsuda and Hirofumi Noguchi and Tetsuji Mutoh and Masahiro Mutoh and Haruhiko Koseki and Masakazu Namihira and Kinichi Nakashima",
year = "2019",
month = "6",
day = "1",
doi = "10.1016/j.neures.2018.05.007",
language = "English",
volume = "143",
pages = "31--43",
journal = "Neuroscience Research",
issn = "0168-0102",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Np95/Uhrf1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain

AU - Murao, Naoya

AU - Matsubara, Shuzo

AU - Matsuda, Taito

AU - Noguchi, Hirofumi

AU - Mutoh, Tetsuji

AU - Mutoh, Masahiro

AU - Koseki, Haruhiko

AU - Namihira, Masakazu

AU - Nakashima, Kinichi

PY - 2019/6/1

Y1 - 2019/6/1

N2 - Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis. Specific ablation of Np95 in adult NS/PCs (aNS/PCs) led to a decrease in their proliferation and an impairment of neuronal differentiation and to suppression of neuronal maturation associated with the impairment of dendritic formation in the hippocampal DG. We also found that deficiency of Np95 in NS/PCs increased the expression of tumor suppressor genes p16 and p53, and confirmed that expression of these genes in NS/PCs recapitulates the phenotype of Np95-deficient NS/PCs. Taken together, our findings suggest that Np95 plays an essential role in proliferation and differentiation of aNS/PCs through the regulation of tumor suppressor gene expression in adult neurogenesis.

AB - Adult neurogenesis is a process of generating new neurons from neural stem/precursor cells (NS/PCs) in restricted adult brain regions throughout life. It is now generally known that adult neurogenesis in the hippocampal dentate gyrus (DG) and subventricular zone participates in various higher brain functions, such as learning and memory formation, olfactory discrimination and repair after brain injury. However, the mechanisms underlying adult neurogenesis remain to be fully understood. Here, we show that Nuclear protein 95 KDa (Np95, also known as UHRF1 or ICBP90), which is an essential protein for maintaining DNA methylation during cell division, is involved in multiple processes of adult neurogenesis. Specific ablation of Np95 in adult NS/PCs (aNS/PCs) led to a decrease in their proliferation and an impairment of neuronal differentiation and to suppression of neuronal maturation associated with the impairment of dendritic formation in the hippocampal DG. We also found that deficiency of Np95 in NS/PCs increased the expression of tumor suppressor genes p16 and p53, and confirmed that expression of these genes in NS/PCs recapitulates the phenotype of Np95-deficient NS/PCs. Taken together, our findings suggest that Np95 plays an essential role in proliferation and differentiation of aNS/PCs through the regulation of tumor suppressor gene expression in adult neurogenesis.

UR - http://www.scopus.com/inward/record.url?scp=85048007322&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85048007322&partnerID=8YFLogxK

U2 - 10.1016/j.neures.2018.05.007

DO - 10.1016/j.neures.2018.05.007

M3 - Article

VL - 143

SP - 31

EP - 43

JO - Neuroscience Research

JF - Neuroscience Research

SN - 0168-0102

ER -