NEWS
July 2026
・Taeko gave an oral presentation (selected) at the Neurogenesis and Repair 2026 (15th, Toronto).
・Taeko gave a poster presentation at the Neuro 2026 (30th, Kobe, Japan).
June 2026
・Rina, Yusuke, Takuya, and He gave poster presentations at the WINGS-LST/SPRING-GX meeting (26th).
May 2026
・Tianquan gave a flash talk and poster presentation at the 53rd IMR Symposium (28-29th).
Apr 2026
・Yukiko joined our group (2nd). Welcome!!
・Rina gave a poster presentation at the Cold Spring Harbor Conferences Asia (Suzhou, China, 7th)
Feb 2026
・Rina and Yusuke gave oral and poster presentations at the 22nd annual meeting of the Adult Neurogenesis Conference (Kochi, 28th). Yusuke received the Young Investigator Award (oral presentation). Congratulations!!
Dev 2025
Zhang’s paper has been posted on bioRxiv. (17th) doi: https://doi.org/10.64898/2025.12.16.694780
Nov 2025
・Rina gave a poster presentation, and Taeko organized a symposium and gave a talk at the 98th annual
meeting of the Japanese Biochemical Society in Kyoto (4th).
・We participated in a softball match at our institute (12th).
・Taeko gave a talk at the 19th annual meeting of the biochemical society for stress response in Kanazawa
(14th).
Oct 2025
・Wei and William joined our group as research students. Welcome!!
・Professor Dieter Chichung Lie kindly visited our lab (28th).
・Rina, He, Yusuke, Takuya and Tianquan gave poster presentations, and Taeko gave a talk in the
international conference ISPO2025 in Nara (from the 30th to November 2nd).
Sep 2025
・He and Takuya presented posters, and Taeko gave an invited lecture at the 68th Annual Meeting of
the Japanese Society for Neurochemistry (11-13th, Nagoya)
・He completed the Master's program at the Graduate School of Biostudies, Kyoto University (24th).
Congratulations!
Introduction
Our body derived from a fertilized egg comprises about 210 types of cells, totaling 37 trillion. In the body, stem cells create new functional cells and constantly replace them to maintain the body's function.
Recently, it has been revealed that stem cells (neural stem cells) exist in the brain throughout life and can create new neurons.
However, most of the neural stem cells in the adult brain are quiescent (sleeping). How are these sleeping neural stem cells involved in maintaining brain function?
Our group is currently interested in the mechanism of regulation of quiescent neural stem cells.

Research
How is brain function maintained throughout life?
In this increasingly aging society, it is imperative to keep healthy brain functions even in old age. Quiescence in adult neural stem cells might be crucial to addressing this question.
Most adult brain neural stem cells (more than 90%) are quiescent. It remains unclear why so many neural stem cells (NSCs) persist in the quiescent state in the adult brain. Quiescence is essential to avoid precocious exhaustion of neural stem cells, ensuring a sustainable source of available stem cells in a specific niche without senescence throughout the lifespan. Significantly, the reactivation of NSCs from quiescent to proliferating substantially decreases with age.
Intrinsic and extrinsic factors tightly regulate the quiescence of adult NSCs, and diverse signaling from local NSC niches is involved in this process. I aim to reveal the mechanism of adult NSC maintenance from novel viewpoints of the ‘lysosome’ and ‘extracellular stiffness’ and to improve the functional decline of NSCs with age.
I will clarify the molecular and physical mechanisms for maintaining NSCs based on lysosomal control and contribute to developing new therapeutic tools for degenerative brain diseases, such as Alzheimer’s.



Published Papers
Research Papers
Zhang, H., Ishii, K., Shibata, T., Ishii, S., Hirao, M., Lu, Z., Takamura, R., Kitano, S., Miyachi, H., Kageyama, R., Itakura, E. and *Kobayashi, T.
Fluctuation of lysosomal protein degradation in neural stem cells of postnatal mouse brain.
Development. 151, dev202231 (2024)
Park, G., Shin, M., Lee, W. Hotta, A., Kobayashi, T. and *Kosodo, Y.
Direct visualization of the transition status during neural differentiation by dual-fluorescent reporter human pluripotent stem cells.
Stem Cell Reports. 17, 1903-1913. (2022)
Kaise, T., Fukui, M., Sueda, R., Piao, W., Yamada, M., Kobayashi, T., Imayoshi, I. and *Kageyama, R.
Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity.
Genes Dev. 36, 23-37. (2022)
Zhang, J., Uchiyama, J., Imami, K., Ishihama, Y., Kageyama, R. and *Kobayashi,T.
Novel roles of small extracellular vesicles in regulating the quiescence and proliferation of neural stem cells.
Frontiers in Cell and Developmental Biology(2021) 9 | Article 762293
*Kobayashi, T., Piao, W., Takamura, T., Kori, H., Miyachi, H., Kitano, S., Iwamoto, Y., Yamada, M., Imayoshi, I., Shioda, S., Ballabio, A., and *Kageyama, R.
Enhanced lysosomal degradation maintains the quiescent state of neural stem cells.
Nat. Commun. 10, 5446. (2019)
Komori, H., Golden, K. L., Kobayashi, T., Kageyama, R., and *Lee, C.-Y.
Multilayered gene control drives timely exit from the stem cell state in uncommitted progenitors during Drosophila asymmetric neural stem cell division.
Genes Dev. 32, 1–12. (2018)
*Kobayashi, T., Iwamoto, Y., Takashima, K, Isomura, A., Kosodo, Y., Kawakami, K., Nishioka, T., Kaibuchi, K., and *Kageyama, R.
Deubiquitinating enzymes regulate Hes1 stability and neuronal differentiation.
FEBS J. 282, 2475-2487. (2015)
Nagashima, F., Suzuki, I. K., Shitamukai, A., Sakaguchi, H., Iwashita, M., Kobayashi, T., Tone, S., Toida, K., Vanderhaeghen, P. and *Kosodo, Y.
Novel and robust transplantation reveals the acquisition of polarized processes by cortical cells derived from mouse and human pluripotent stem cells.
Stem Cells Dev. 23, 2129-2142. (2014)
Ueo, T., Imayoshi, I., Kobayashi, T., Ohtsuka, T., Seno, H., Nakase, H., Chiba, T. and *Kageyama, R.
The role of Hes genes in intestinal development, homeostasis and tumor formation.
Development. 139, 1071-1082. (2012)
*Kobayashi, T. and *Kageyama, R.
Hes1 regulates embryonic stem cell differentiation by suppressing Notch signaling.
Genes Cells. 15, 689-698. (2010)
*Kobayashi, T., Mizuno, H., Imayoshi, I., Furusawa, C., Shirahige, K. and *Kageyama, R.
The cyclic gene Hes1 contributes to diverse differentiation responses of embryonic stem cells.
Genes Dev. 23, 1870-1875. (2009)
Ishii, A., Kobayashi, T. and *Kageyama, R.
Requirement of multiple lysine residues for the transcriptional activity and the instability of Hes7.
Biochem Biophys Res Commun. 372, 142-6. (2008)
Kobayashi, T., Manno, A. and *Kakizuka, A.
Involvement of valosin-containing protein (VCP)/p97 in the formation and clearance of abnormal protein aggregates.
Genes Cells. 12, 889-901. (2007)
Kobayashi, T., Tanaka, K., Inoue, K. and *Kakizuka, A.
Functional ATPase activity of p97/valosin-containing protein (VCP) is required for the quality control of endoplasmic reticulum in neuronally differentiated mammalian PC12 cells.
J. Biol. Chem. 277, 47358-65. (2002)
Kobayashi, T., Takahashi, Y. and *Ito, K.
Identification of a segment of DsbB essential for its respiration-coupled oxidation.
Molecular Microbiology 39, 158-165. (2001)
Kobayashi, T. and *Ito, K.
Respiratory chain strongly oxidizes the CXXC motif of DsbB in the Escherichia coli dislfide bond formation pathway.
The EMBO Journal. 18, 1192-1198. (1999)
Kobayashi, T., Kishigami, S., Sone, M., Inokuchi, H., Mogi, T. and *Ito, K.
Respiratory chain is required to maintain oxidized states of DsbA-DsbB disulfide bond formation system in aerobically growing Escherichia coli cells.
Proc. Natl. Acad. Sci. USA 94, 11857-11862. (1997)
Review papers
*Kobayashi, T.
Protein homeostasis and degradation in quiescent neural stem cells.
J. Biochem. 175, 481–486. (2024)
*Kobayashi, T. and *Kageyama, R.
Lysosomes and signaling pathways for maintenance of quiescence in adult neural stem cells.
FEBS J. 288, 3082-3093. (2020) State‐of‐the‐Art Review
*Kobayashi, T. and *Kageyama, R.
Expression dynamics and functions of Hes genes in development and diseases.
Curr Top Dev Biol. 110, 263-283. (2014)
Harima, Y., Imayoshi, I., Shimojo, H., Kobayashi, T., and Kageyama, R.
The roles and mechanism of ultradian oscillatory expression of the mouse Hes genes.
Semin Cell Dev Biol. 34, 85-90. (2014)
*Kobayashi, T. and *Kageyama, R.
Hes1 oscillations contribute to heterogeneous differentiation responses in embryonic stem cells.
Genes. 2, 219-228 (2011)
*Kageyama, R., Niwa, Y., Shimojo, H., Kobayashi, T., Ohtsuka, T.
Ultradian oscillations in Notch signaling regulate dynamic biological events.
Curr. Top. Dev. Biol. 92, 311-331. (2010)
*Kobayashi, T. and *Kageyama, R.
Hes1 oscillation: making variable choices for stem cell differentiation.
Cell Cycle. 9, 207-8. (2010)
*Kobayashi, T. and *Kageyama, R.
Dynamic advances in NF-kappaB signaling analysis.
Sci Signal. 2, pe47. (2009)
*Kageyama, R., Ohtsuka, T. and Kobayashi, T.
Roles of Hes genes in neural development.
Dev Growth Differ. 50 Suppl 1, S97-103. (2008)
*Kageyama, R., Ohtsuka, T. and Kobayashi, T.
The Hes gene family: repressors and oscillators that orchestrate embryogenesis. Development. 134, 1243-51. (2007)
Kobayashi, T. and *Kakizuka, A.
Molecular analyses of Machado-Joseph disease.
Cytogenet Genome Res. 100, 261-75. (2003)
Latest Publications
*Kobayashi T.
Protein homeostasis and degradation in quiescent neural stem cells. J. Biochem. 175, 481–486. (2024)
https://academic.oup.com/jb/article/175/5/481/7595742
Zhang, H., Ishii, K., Shibata, T., Ishii, S., Hirao, M., Lu, Z., Takamura, R., Kitano, S., Miyachi, H., Kageyama, R., Itakura, E. and *Kobayashi, T.
Fluctuation of lysosomal protein degradation in neural stem cells of postnatal mouse brain.
Development. 151, dev202231 (2024)
https://doi.org/10.1242/dev.202231
Park, G., Shin, M., Lee, W. Hotta, A., Kobayashi, T. and *Kosodo, Y.
Direct visualization of the transition status during neural differentiation by dual-fluorescent reporter human pluripotent stem cells. Stem Cell Reports. 17, 1903-1913. (2022)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481873/
Kaise, T., Fukui, M., Sueda, R., Piao, W., Yamada, M., Kobayashi, T., Imayoshi, I. and *Kageyama, R.
Functional rejuvenation of aged neural stem cells by Plagl2 and anti-Dyrk1a activity.
Genes Dev. 36, 23-37. (2022)
http://genesdev.cshlp.org/content/early/2021/12/14/gad.349000.121
Zhang, J., Uchiyama, J., Imami, K., Ishihama, Y., Kageyama, R. and *Kobayashi,T.
Novel roles of small extracellular vesicles in regulating the quiescence and proliferation of neural stem cells.
Frontiers in Cell and Developmental Biology(2021) 9 | Article 762293
https://www.frontiersin.org/articles/10.3389/fcell.2021.762293
*Kobayashi, T., Piao, W., Takamura, T., Kori, H., Miyachi, H., Kitano, S., Iwamoto, Y., Yamada, M., Imayoshi, I., Shioda, S., Ballabio, A., and *Kageyama, R.
Enhanced lysosomal degradation maintains the quiescent state of neural stem cells.
Nat. Commun. 10, 5446. (2019)
Current member

Kobayashi, Taeko
Associate professor in the Institute of Medical Science, The University of Tokyo
Hometown: Nara
BA in Science, Nara Women's University.
MA in Science, Kyoto University.
Ph.D. in Science, Kyoto University.
Message
Research is fascinating because I can test my ideas immediately. If you are interested in our study, please contact me anytime!

Deng, Shenghuan
Graduate student (D3) in the Graduate School of Frontier Sciences, The Univ. of Tokyo; Hometown: China
BA in Bengbu Medical College.
MA in Tokyo Medical and Dental University, Japan.
She joined our group in Nov. 2023.
Message
Exploring neural stem cells is fascinating, and I'm excited to discover their mysteries and embrace the challenge.

Onishi, Rina
Graduate student (D2) in the Graduate School of Medicine, The Univ. of Tokyo.
Hometown: Hyogo
BA in Engineering, Tottori University.
MA in the Graduate School of Biostudies, Kyoto Univ.
She joined our group in April 2023.
Message
I want to study every day and make progress in this pleasant environment.

Kihara, Yusuke
Graduate student (D2) in the Graduate School of Pharmaceutical Science, The Univ. of Tokyo. Hometown: Fukuoka
BA in Agriculture and Life Science, Hirosaki University. MA in the Graduate School of Biostudies, Kyoto Univ.
He joined our group in April 2023.
Message
I want to progress by devoting myself to my project step by step!

Nitta, Takuya
Graduate student (D2) in the Graduate School of Pharmaceutical Science, The Univ. of Tokyo. Hometown: Wakayama
BA in Pharmaceutical Sciences, Tokushima Univ. MA in the Graduate School of Biostudies, Kyoto Univ.
He joined our group in April 2023.
Message
I'm new to life science experiments and will do my best!!!

Cui, Tianquan
Graduate student (D2) in the Graduate School of Medicine, The Univ of Tokyo.
Hometown: China. BA in China Medical University and Queen’s University Belfast. MA in University College London. He joined in Oct. 2024.
Message
Exploring the field of NSCs is extremely exciting! My ideal goal is to harness the potential to restore healthy brain function under different pathological and physiological conditions. I am so honored to join in the Kobayashi group, and will do my best to learn new skills and apply them in future.

Zhang, He
Graduate student (D1) in the Graduate School of Pharmaceutical Science, The Univ. of Tokyo. Hometown: China.
BA in Hunan Agricultural University and the University of Greenwich. MA in the Graduate School of Biostudies, Kyoto Univ. He joined our group in April 2022.
Message
good good study, day day up

Ziyi, Wei
Graduate student (D1) in the Graduate School of Medicine, The Univ of Tokyo.
Hometown: China.
BA in Basic Medical Sciences, Sichuan University, China.
She joined our group in Oct 2025.
Message
Never abandon your pursuit for the sake of one failure

BURRIS, William Parker
Research student in the Graduate School of Pharmaceutical Science, The Univ. of Tokyo.
Hometown: Colorado
BA in the University of New Mexico.
He joined our group in Oct 2025.
Message
I am excited to research NSCs because these fascinating cells will help us understand how to keep brains healthy.

Fujimori, Toshihiro
Technical Assistant
Third-year student at the Faculty of Science, Tokyo University of Science.
Hometown: Tokyo.
He joined our group in April 2025.
Message
I will do my best!
I aim to absorb new knowledge daily through technical support and develop it into my skills.
Alumuni

Jingtian Zhang
She was a master's course student in our group at Kageyama Lab and from Harbin, China. She graduated from the global course of GSB in the fall of 2021. She always did her best in experiments, discussions, and thesis writing. She successfully finished her work by publishing her excellent paper. Congratulations.
Message
Prepare for the worst and hope for the best! I feel so lucky to have the chance to work with Kobayashi sensei. She was being patient and gentle in correcting my mistakes and in teaching me techniques. Meanwhile, she is always being supportive and genuinely cares about my well-being. It has been a happy experience working with her.

Karan Ishii
In our group, she was a technical assistant from Oct. 2020 to Jul. 2022.
She graduated from UCLA with B.A.
Especially from the spring in 2022, she guided newcomers a lot in experiments, research, and activities of Kyoto while conducting her own experiments.
Thanks.
Message
I'm honored to be able to work with Dr. Kobayashi and love learning every day! Some of my favorite things are: skiing, Thai food, the Lake Biwa Canal, summer camp, and the P200 pipette.

Urbi Paul
She was a summer student of AMGEN Scholar from Jun to Aug 2022.
She is an undergraduate student at Indian Institute of Science Education and Research in Kolkata, India.
She was highly motivated to do research, questions, and discussions and enjoyed them. She finished her first presentations very well, with many experimental results.
Message
I joined Kobayashi sensei's group as an Amgen scholar and I have learned a lot. All the members were very kind and supportive. As a beginner in research, I asked many questions that were patiently answered. Kobayashi sensei's hardworking attitude motivates me and inspires me to take up research as a career in the near future.

