NEWS
December 2024
・Yusuke gave a poster presentation at the Ribosome meeting 2024 in Japan. (December 2, our institute)
Ribosome heterogeneity in neural stem cells.
November 2024
・Kobayashi lectured at the 18th annual meeting of the Biomedical Society for Stress Response, Japan.
(November 2, Miyazaki)
・Lu gave a poster presentation at the 97th annual meeting of the Japanese Biochemical Society.
(November 6, Yokohama)
Delta/Notch-like EGF-related receptor plays a role in regulating the proliferation of neural stem cells.
・Rina presented her poster at the 47th Annual Meeting of the Molecular Biology Society of Japan.
(November 29, Fukuoka) Analysis of mitophagy activity in quiescent neural stem cells.
・Zhang and Takuya gave poster presentations at the 21st Annual Meeting of the Adult Neurogenesis
Conference. Takuya won the Young Investigator Award! (November 30, Tokyo University of Science)
Identification of crucial factors for neural stem cell proliferation. (Takuya Nitta)
The regulation of neurogenesis and neural stem cells quiescence in mouse brain（Zhang)
October 2024
・Tianquan Cui joined our group as a research student. Welcome!
・Zhang gave a poster presentation at the 19th International Symposium of the Institute Network for
Biomedical Sciences (October 10-11, Sendai).
September 2024
・Zhang and Kihara gave poster presentations at the group meeting (September 18-20, Atami).
・Students from Ibaraki Prefectural Midorioka High School visited our lab. (September 30).
https://www.ims.u-tokyo.ac.jp/imsut/jp/relations/page_00062.html
・Lu completed his master's course at the Graduate School of Biostudies, Kyoto University. (September 24)
June 2024
・Kobayashi gave a poster presentation and a short talk at EUROGENESIS 5th meeting - Adult Neurogenesis
in Physiology and Disease. (June 12-14, Bordeaux, France)
Lysosomal proteolysis monitor to measure lysosomal activity in neural stem cells of the adult mouse brain.
https://eurogenesis.sciencesconf.org/
・Kihara (M2) gave a poster presentation and an oral presentation at JPROS2024 (22nd JHUPO) & JSCP
20th (June 26-28, Aomori). Elucidation of the mechanisms of translation regulation in neural stem cells.
May 2024
・The 2nd symposium on "Shin-Biology Regulated by Protein Lifetime" was held in our institute (May 9).
・Kobayashi's review was opened in JB.
Protein homeostasis and degradation in quiescent neural stem cells
April 2024
・We saw cherry blossoms at the Tokyo Metropolitan Teien Art Museum on the 5th.
・Deng was admitted to the doctoral course of the Graduate School of Frontier Sciences (April 12).
Congratulations!
・We participated in our institute's cherry-blossom (welcome) party (April 18).
March 2024
・Our lab's desk room was rearranged (March 27).
February 2024
・Zhang's paper has been published in Development! (February 14)
Development (2024) 151 (4): dev20223. https ://doi.org/10.1242/dev.202231
・Kobayashi gave talks at the AMED Meeting (February 7, Tokyo) and the Protein Lifetime meeting
(February 11, Kakegawa).
・Zhang gave an oral presentation, and Lu, Onishi, Kihara, and Nitta gave poster presentations at the the
Protein Lifetime meeting (February 10-12, Kakegawa). They all did a great job.
January 2024
・Zhang's LyMo paper has been accepted by Development! (January 17). Congratulations!
・Kobayashi gave a talk at the 1st Meeting of Multicellular Quiescence (Philostasis). (Quiescence regulation
in adult neural stem cells) (January 16, Okinawa)
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 6, 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 2, Hakata)
・Students from Midorigaoka high school in Ibaraki visited our lab! (November 6)
・Deng Shenghuan joined our group. Welcome!
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
Alumuni
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