Our research is focused on the stem cell biology, especially on the generation, proliferation, maintenance and differentiation of neural stem cells.

We are interested in how neural stem cells are selected and induced from precursor cells with broader potency (or pluripotent cells) in very early mouse embryos. We recently discovered that epigenetic regulation plays important roles in the generation of neural stem cells.

It is well known that neural stem cells exist in adult mammalian brains, including humans, and provide new neurons in the olfactory bulb and the dentate gyrus of hippocampus throughout the lifetime of the animal. We are studying the behaivior of neural stem cells in pathological conditions using animal models for chronic demyelination or depression. Our research might provide in the future insight into the pathogenesis of those diseases and the development of new treatment.

What's new...

2025.10.22
Our Gcm1 paper has been accepted by iScience. Many Congratulations!!

2025.5.1
Dr. Sayuki Takara, a new Assistant Professor, comes to our Department. Hope she would conduct our macaque monkey project.

2024.6.30
Asmaa has moved to NYC as a postdoc in Dr. Meelad Dawlaty's Lab at Albert Einstein College of Medicine. Many Good Luck!

2024.4.3
Asmaa wrote a review paper regarding fucosyltransferase in the Trends in Glycoscience and Glycotechnology.

2023.9.5
Zakiyyah published her PhD work in the Journal of Physiological Sciences. Congratulations!

2022.6.6
Asmaa's PhD work, analyzing the brain of Fut9 KO mice has been accepted for publication in the Neurochemical Research. Congratulations! She continues neural development and epigenetics research as a postdoc.

2022.3.18
Another Malaysian graduate student, Azrah, joined our laboratory.

2021.3.31
Koyama-sensei retired from the University but may continue research activities. Check it!

2020.7.4
Our latest research mainly conducted by undergrad students has been accepted by the Cerebral Cortex. Many Congratulations!!

2020.1.10
Ken's manuscript studying the effect of neonatal stress on neural stem cells in adulthood has been accepted by the Frontiers in Neuroscience. Congratulations!

Selected Publications

Hayashi Y, Abdullah A, Fuke S, Mohd Ariffin NAF, Daun KA, Morimura N, Nakabayashi K, Tatsumoto S, Go Y, Hosoya T, Hitoshi S (2025) Glial cells missing 1 triggers gliosis and angiogenesis after neonatal brain injury. iScience 28, 113860   

Abdullah A, Hayashi Y, Morimura N, Kumar A, Ikenaka K, Togayachi A, Narimatsu H, Hitoshi S (2022) Fut9 deficiency causes abnormal neural development in the specific layer of the brain and retina. Neurochem Res 47, 2793–2804  

*Tanaka A, *Ishida S, *Fuchigami T, Hayashi Y, Kuroda A, Ikenaka K, Hitoshi S (2020) Life-long neural stem cells are fate-specified at an early developmental stage. Cerebral Cortex 30, 6415–6425 (*, equal contribution)

Daun KA, Fuchigami T, Koyama N, Maruta N, Ikenaka K, Hitoshi S (2020) Early maternal and social deprivation expands neural stem cell population size and reduces hippocampus/amygdala-dependent fear memory. Front Neurosci 14, 22

Morimura N, Yasuda H, Yamaguchi K, Katayama KI, Hatayama M et al. (2017) Autism-like behaviours and enhanced memory formation and synaptic plasticity in Lrfn2/SALM1-deficient mice.
Nature Communications 8, 15800

*Naruse M, *Ishino Y, Kumar A, Ono K, Takebayashi H, Yamaguchi M, Ishizaki Y, Ikenaka K, Hitoshi S (2015) The dorsoventral boundary of the germinal zone is a specialized niche for the generation of cortical oligodendrocytes during a restricted temporal window. Cerebral Cortex 26, 2800-2810 (*, equal contribution)

*Zheng L-S, *Hitoshi S, *Kaneko N, Takao K, Miyakawa T, Tanaka Y, Xia H, Kalinke U, Kudo K, Kanba S, Ikenaka K, Sawamoto K (2014) Mechanisms for interferon-α-induced depression and neural stem cell dysfunction. Stem Cell Reports 3, 74-83 (*, equal contribution)

*Ishino Y, *Hayashi Y, Naruse M, Tomita K, Sanbo M, Fuchigami T, Fujiki R, Hirose K, Toyooka Y, Fujimori T, Ikenaka K, Hitoshi S (2014) Bre1a, a histone H2B ubiquitin ligase, regulates the cell cycle and differentiation of neural precursor cells. J Neurosci 34, 3067-3078 (*, equal contribution)

Kumar A, Torii T, Ishino Y, Muraoka D, Yoshimura T, Togayachi A, Narimatsu H, Ikenaka K, Hitoshi S (2013) The Lewis X-related α1,3-fucosyltransferase, Fut10, is required for the maintenance of stem cell populations. J Biol Chem 288, 28859-28868

Hitoshi S, Ishino Y, Kumar A, Jasmine S, Tanaka KF, Kondo T, Kato S, Hosoya T, Hotta Y, Ikenaka K (2011) Mammalian Gcm genes induce Hes5 expression by active DNA demethylation and induce neural stem cells. Nat Neurosci 14, 957-964

Higashi M, Maruta N, Bernstein A, Ikenaka K, Hitoshi S (2008) Mood stabilizing drugs expand the neural stem cell pool in the adult brain through activation of Notch signaling. Stem Cells 26, 1758-1767

Hitoshi S, Alexon T, Tropepe V, Donoviel D, Elia AJ, Nye JS, Conlon RA, Mak TW, Bernstein A, van der Kooy D (2002) Notch pathway molecules are essential for the maintenance, but not for the generation, of mammalian neural stem cells. Genes & Dev 16, 846-858

and more...