Department of Basic Medical Sciences,
The Institute of Medical Science, The University of Tokyo

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Kobayashi Group

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The Institute of Medical Science
The University of Tokyo

Kobayashi Group

news

NEWS

December 2023

・Kobayashi lectured at the symposium "Dysregulation of Protein/RNA Homeostasis in Neuronal Function - From Neurogenesis to Neuropathology -" at the 46th annual meeting of the Molecular Biology Society of Japan. (Functional fluctuation of lysosomal protein degradation in neural stem cells of the postnatal brain, December 6th, Kobe)

November 2023

・Kobayashi gave a lecture at the symposium "The Science of Protein Lifespan" at the 96th annual meeting of the Japanese Biochemical Society. (Analysis of lysosomal proteolysis in neural stem cells in the brain; November 2nd, Hakata)

・Students from Midorigaoka high school in Ibaraki visited our lab! (November 6th)

・Ms. Deng Shenghuan joined our group. Welcome!

October 2023

・Kobayashi group started our research at the University of Tokyo! (October 1st)

・Mr. Zhang became a master course student! (October 1st)

・Kobayashi gave a special lecture at the 64th Annual Meeting of the Japanese Society for Inherited Metabolic Diseases (Lysosomal regulation in adult neural stem cells; October 6th, Osaka)

September 2023

・Kobayashi group moved to the Institute of Medical Science, the University of Tokyo.
https://www.u-tokyo.ac.jp/focus/ja/people/k0001_05361.html
https://www.ims.u-tokyo.ac.jp/imsut/jp/

August 2023

・Kobayashi organized and chaired an international symposium with Prof. Sawamoto of Nagoya City University on "Elucidating Molecules and Tissue Environment for Functional Regeneration of the Aged Brain" at the 46th Annual Meeting of the Japan Neuroscience Society. (Talk: Lysosomal and proteostatic regulation in adult neural stem cells; Sendai, August 3rd)

・Kobayashi talked at the kick-off symposium on "Shin-Biology Regulated by Protein Lifetime", organized by Grant-in-Aid for Transformative Research Areas (A), MEXT Japan. (Protein Lifespan Dynamics in Neural Stem Cells; Tokyo, August 7th)

July 2023

・Our new review, " Lysosomal function in neural stem cells," was published in Jikken Igaku

DOI: 10.18958/7277-00001-0000512-00

June 2023

・Mr. Zhang gave a poster presentation at the 75th Annual Meeting of the Japan Society for Cell Biology. (Lysosomal activity fluctuation in neural stem cells in the brain; Nara, June 30th)

・Kobayashi talked at the 24th Symposium of Graduate School of Biostudies. (Lysosomal function in adult neural stem cells; Kyoto, June 22nd)

・Our report of Kyoto Univ SPIRIS is open on the web. (Brain rejuvenation through activation of neural stem cells based on understanding of mechanistic and biochemical factors)

https://research.kyoto-u.ac.jp/spirits/en2020/en2020_016/

May 2023

We enjoyed the Softball match of our department @ Gosho grounds in Kyoto Gyoen National Garden.

April 2023

Four new graduate students joined our group: Ms. Onishi, Mr. Kihara, Mr. Nitta (master course), and Ms. Peilin (doctor course). Welcome!!!!

March 2023

・Kobayashi gave a lecture at International symposium on neural development and disease. (Monitoring lysosomal protein degradation in neural stem cells of the brain; Kyoto, March 16th)

・Ms. Takamura graduated from Kyoto University. (March 24th)

January 2023

Kobayashi gave a lecture at the Medical Institute of Bioregulation, Kyusyu University. (Regulation of proteostasis in adult neural stem cell quiescence, January 26th)

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.

introduction

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

bioRxiv(2023), https://www.biorxiv.org/content/10.1101/2023.05.12.540513v1

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. 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

bioRxiv(2023), https://www.biorxiv.org/content/10.1101/2023.05.12.540513v1

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)

https://doi.org/10.1038/s41467-019-13203-4

See All

Latest Publications

people

Current member

Taeko Kobayashi

Associate professor in the Graduate School of Biostudies, Kyoto Univ.

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!

Lu Zhou

Graduate student (M2) in the Graduate School of Biostudies, Kyoto Univ.

Hometown: China.

BA in Zhejiang University

He joined our group from Oct. 2022.

Message

Feeling fun of learning more about neural stem cells and trying to discover more about them. I feel so fortunate to work with Kobayashi sensei, and I’ll try my best to respond to her teachings throughout my study career.

Rina Onishi

Graduate student (M1) in the Graduate School of Biostudies, Kyoto Univ.

Hometown: Hyogo

BA in Engineering, Tottori University.

She joined our group from April 2023.

Message

I want to study every day and make progress in this pleasant environment.

Yusuke Kihara

Graduate student (M1) in the Graduate School of Biostudies, Kyoto Univ.

Hometown: Fukuoka

BA in Agriculture and Life Science, Hirosaki University.

He joined our group from April 2023.

Message

I want to progress by devoting myself to my project step by step!

Takuya Nitta

Graduate student (M1) in the Graduate School of Biostudies, Kyoto Univ.

Hometown: Wakayama

BA in Pharmaceutical Sciences, Tokushima University.

He joined our group from April 2023.

Message

I'm new to life science experiments and will do my best!!!

Zhang He

Graduate student (M1) in the Graduate School of Biostudies, Kyoto Univ.

Hometown: China.

BA in Hunan Agricultural University and　the University of Greenwich. He joined our group from April 2022 as RS.

Message

Research student now, but trying to become useful. Great fun of learning lab skills and data analysis every single day. It's a great honor for me to study with Kobayashi sensei.

Deng Shenghuan

Technical Assistant

Hometown: China

BA in Bengbu Medical College.

MA in Tokyo Medical and Dental University, Japan.

She joined our group from Nov. 2023.

Message

・・・

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.

Risa Takamura

She was a office assistant of Kobayashi group from 2020 to 2023, and graduated from Faculty of Medicine, Kyoto University at March 2023.

She helped a lot of our experiments from plasmid construction to stem cell culture.

She is in the middle of this picture.

Message

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B2652087-7F20-4218-8926-15232BE80594_1_105_c_edited.jpg

Peilin Zou

She was a PhD student in Kobayashi group from April to August in 2023.

She was gentle and highly motivated by brain research. She started her new project in Sep. 2023 at Prof. Kengaku Lab of the GSB, Kyoto University. She is the second person from the right rear on the photo at our last party in Kyoto.

Message

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Tatsuya Shibata

He is a graduate student of the Graduate School of Agriculture, Kyoto University　and studies archetecuture. He worked as an office assistant in our group from Sep 2021 to Sep 2023. He helped a lot of

data analysis from huge number of results using Python. He is the most left person on the photo.

Message

I spend many days struggling with the PC in the lab.

Yuki Murai

He is an undergraduate student at Kyoto University, Faculty of Medicine. He participated in our research from Aug. 2022 to Aug. 2023 and contributed a lot. He is highly motivated since he wants to be involved in research and techniques to improve symptoms of incurable brain diseases such as cognitive dysfunction and psychiatric disorders.

Message

I am still an undergraduate student, but always excited to study in this lab. I would like to work as hard as possible to make my pathway as a researcher!!.

Marika Hirao

PhD. She was a research assistant in Kobayshi group from June 2022 to Sep 2023. She supported young students and our research, especially for mouse maintenance. She helped us even after our members moved to Tokyo. Thanks a lot! She is the rightmost person in our Kyoto lab after packing for moving.

Message

I have a blank and limited time, but I would happily contribute as much as possible.

Kaori Mori

She graduated from Kyoto Women's University. She was a secretory in Kobayashi group from April 2022 to Sep. 2023.

She is a certified financial planner and

her advice was very helpful.

Thanks a lot!!

She is the leftmost person in the photo.

Message

I will do my best to support everyone.

Contact

Taeko Kobayashi

4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, JAPAN

The Institute of Medical Science, The University of Tokyo

Tel: +81-3-5449-5257

e-mail:

kobayashi-tk@g.ecc.u-tokyo.ac.jp

takobayas@gmail.com

Department of Basic Medical Sciences, The Institute of Medical Science, The University of Tokyo

Kobayashi Group

The Institute of Medical Science The University of Tokyo

Kobayashi Group

NEWS

Introduction

Research

Published Papers

Research Papers

Review papers

Latest Publications

Current member

Alumuni

Contact

e-mail:

Department of Basic Medical Sciences,
The Institute of Medical Science, The University of Tokyo

The Institute of Medical Science
The University of Tokyo