Now, researchers from Japan have found an overlapping two-factor system that plays an important role in controlling when and how these cells differentiate. In a study published this month in Cell Reports, researchers from The University of Osaka have revealed that two proteins with very similar functions are key regulators of early steps in cellular development and maturation.

Embryonic stem cells can develop into all the different types of cells present in the adult body, from brain cells to liver cells, through a process called differentiation. This process is tightly regulated by activating and repressing factors that bind to the promoters of developmental genes to maintain them in a ‘poised’ state, where these genes can either be switched on or kept off as needed.

“A key mechanism for inhibiting the expression of genes associated with stem cell differentiation involves repressor complexes such as CoREST,” says lead author, Takamasa Ito. “However, it remains unclear how CoREST-mediated repression is stably maintained and which other factors help in repressing expression of these genes.”

To explore this, the researchers tested the role of two proteins, RLF and ZFP292, which previous studies had suggested may help regulate stem cell gene expression. They looked at where these factors bound themselves across the genome and deleted these factors, both individually and together, to determine the effect on gene expression.

“The results were very striking,” explains senior author, Chikashi Obuse. “We found that RLF and ZFP292 play virtually the same role, in that they stabilize the CoREST complex at gene promoters in embryonic stem cells to repress gene expression.”

The presence of either RLF or ZFP292, or both together, at these promoters prevented stem cells from drifting toward differentiation. When these proteins were lost, promoters that were normally repressed became active, leading to the expression of genes associated with differentiation.

“Our results show that RLF and ZFP292 modulate the activity of the CoREST complex to carefully control gene expression in stem cells,” says Ito.

These findings may lead to the development of new techniques for maintaining stem cell quality for research and clinical applications. They also help advance our understanding of diseases caused by dysregulated gene expression and could potentially be applied to develop new treatments.

Overview of the study.
Left: In wild-type cells, RLF/ZFP292 support the proper function of the CoREST complex, leading to the removal of active histone marks and preventing excessive expression of differentiation-associated genes.
Right: In the absence of RLF/ZFP292, CoREST complex function is impaired, resulting in an increase in active histone marks and elevated expression of differentiation-associated genes. Consequently, the undifferentiated state cannot be maintained, and cells undergo differentiation.

The article, “RLF/ZFP292 stabilize CoREST-linked LSD1 engagement at bivalent promoters to safeguard pluripotency,” was published this month in Cell Reports at DOI: https://doi.org/10.1016/j.celrep.2026.117293

Related links

• Department of Biological Sciences, Laboratory of Genome Structure and Function

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• ResOU（Research at Osaka University）website

A total of 18 participants attended (7 undergraduate students from the School of Science, 9 graduate students from the Graduate School of Science, 1 undergraduate and 1 graduate student from other schools.). The workshop provided an intensive learning opportunity for participants from a wide range of disciplines and academic levels, covering the full process from AI fundamentals to data collection, training, and implementation.

On the first day, participants learned the basics of AIoT and edge AI, including the fundamental concept of on-device inference, and then proceeded with the setup of the AMB82-mini. They worked on introductory tasks such as audio classification and image classification, and also learned about recent trends and demonstrations in the fields of vision and audio.

On the second day, the program focused on the data preparation process required for implementation, including data collection using the device. In the final session, participants implemented their systems on mini cars and took part in a time-trial race. The event concluded with a lively atmosphere, as participants cheered and compared the different behaviors of the cars.

We would like to express its sincere gratitude to the faculty members and student tutors from NTNU for their invaluable cooperation and support in making this workshop possible.

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They were welcomed by Prof. Tadashi Kondo, Dean of the Graduate School of Science; Prof. Takashi Kubo, Vice Dean; Prof. Atsushi Takahashi, Vice Dean and Chair of the International Exchange Committee; and Lecturer Yuri Kamon, a member of the International Exchange Committee. During the meeting, the participants exchanged views on future collaboration and on a joint symposium scheduled to be held at the University of Osaka in October this year.

In the afternoon of the same day, a research presentation session was held, featuring presentations by two NSYSU faculty members and four students interested in the Double Degree Program (DDP). Faculty members from our Graduate School in related fields also attended, and the session provided a meaningful opportunity for academic exchange through lively questions and discussion. In addition, a laboratory tour was organized after the session, helping the visitors deepen their understanding of our research environment.

Building on the discussions during this visit, we will continue preparations for the successful joint symposium and further strengthen the cooperative relationship between the two universities.

【visitors】
Prof. Jyh-Tsung Lee, Dean, the College of Science
Prof. May-Ru Chen, Associate Dean, the College of Science
Associate Prof. Cheng-Chau Chiu, Associate Vice President for Academic Affairs
Assistant Prof. Chung-Hsin Yang, Assistant Professor, the College of Science
Prof. Toshio Kasai, the College of Science

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Period: From Wednesday, August 12 to Friday, August 14, 2026.

Researchers, as part of a major international collaboration, reported evidence hinting at the existence of a never-before-seen but predicted exotic bound state known as an η′-mesic nucleus. These valuable findings will be published this month in Physical Review Letters.

Physicists have theorized that under certain conditions, short-lived particles called mesons – which only exist for less than ten-millionth of a second – can become temporarily trapped inside a nucleus, forming an exotic bound system. Measuring mesic nuclei could help scientists understand how the strong nuclear force, which binds atomic nuclei together, behaves and how the vacuum structure changes in extremely high-density environments.

“One particle of particular interest is the η′ meson,” says senior author Kenta Itahashi. “It is unusually heavy compared with related particles, and physicists expect that its mass changes when it exists inside nuclear matter. Observing this phenomenon would provide valuable information about how particle masses are generated in the universe.”

To search for the η′-mesic nuclei, the international collaboration carried out a high-precision experiment using a powerful particle accelerator in GSI Helmholtzzentrum für Schwerionenforschung, Germany. They utilized a beam of high-energy protons bombarded on a carbon target to produce η′-mesic states. The energetic proton beam excites the carbon nucleus, producing η′ mesons, which form a bound state with the carbon nucleus with a certain probability. The excitation energies of the carbon nuclei were measured by analyzing the energy of deuterons –the simplest atomic nucleus made of one proton and one neutron– produced forward in the reaction using a high-resolution spectrometer, Fragment Separator (FRS). Researchers employed a special detector called WASA, which was originally developed and constructed in Uppsala, Sweden, to selectively measure high-energy protons that get out from the target, looking for signs that an η′ meson had been created and captured inside the nucleus, otherwise known as decay signals. 

“With our new experimental setup combining the FRS and the WASA, we can identify structures in the data that match theoretical signatures of η′-mesic nuclei,” explains lead author Ryohei Sekiya. “Our analysis suggests that these bound states were indeed formed.”

The resultant excitation spectrum of the carbon nucleus measured in the experiment is displayed in Fig, indicating possible formation of the η′-mesic nuclei. The team’s findings indicate that the mass of the η′ meson may decrease inside nuclear matter, supporting theoretical predictions and providing rare experimental insight into how the properties of particles change in super high-density environments.

“Our measurements provide important new clues about how mesons behave in nuclear matter,” says Itahashi. “This brings us closer to answering deep, fundamental questions about how matter acquires mass, as well as how the vacuum structure changes inside atomic nuclei.”

Future experiments are planned to increase the precision of measurements and search for additional decay signals that could confirm the existence of η′-mesic nuclei. As researchers continue their search, each new result furthers our understanding of the fundamental physical laws that govern the universe.

Excitation-energy spectrum of the carbon-11 nucleus obtained in the present experiment. The excitation energy on the horizontal axis is defined such that zero corresponds to the production of an η′ meson at rest in vacuum. Negative values correspond to bound states of the η′ meson and the nucleus. The circles represent the experimental data, and the vertical bars indicate statistical uncertainties. The solid curve shows the theoretical spectrum that best reproduces the experimental data, while the dotted curve represents the estimated contribution from background processes. The two observed peak structures suggest the existence of η′ meson bound states in an inner (blue) and outer (blue) nuclear orbits in the carbon-11 nucleus.

The article, “Excitation Spectra of the ¹²C(p,d) Reaction near the η’-Meson Emission Threshold Measured in Coincidence with High-Momentum Protons,” will be published in Physical Review Letters at https://doi.org/10.1103/6vsl-ng7x
This article has been selected for “Featured in Physics” at https://journals.aps.org/prl/highlights.

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Graduate Admissions

This award was established in June 2022 to encourage graduate students who have achieved outstanding research results and other notable achievements each academic year.

This year, four graduate students received this award.

Congratulations!

However, in a recent study published in PNAS, researchers from The University of Osaka have revealed that circadian clock oscillation in cyanobacteria is controlled by factors intrinsic to one of the proteins that controls it, in a manner that is unaffected by environmental conditions.

Even the smallest, photosynthetic organisms have internal clocks, including cyanobacteria. These microorganisms are vital for aquatic environments, agriculture, and biotechnology. Given their vitality, it is even more important to ensure the correct timing of biological processes for photosynthesis during the day, and respiration at night.

Cyanobacteria are known to possess the simplest known circadian clock, involving only three primary proteins: KaiA, B, and C. It was these proteins that were the focus of the investigation.

“Though the cyanobacterial circadian clock is very simple, and can be reconstructed with three proteins, we still wanted to understand how these simple elements work together,” says lead author, Kumiko Ito-Miwa. “It is critical to understand how the reliability of the circadian rhythm is maintained under different environmental conditions, as it affects an incredibly wide variety of cellular processes.”

To do this, the researchers examined more than 20 mutations in the KaiC clock protein, with disturbed clock periods ranging from 15 to 60 hours. Through this, they were able to demonstrate that the circadian clock could maintain accurate timekeeping both in vitro and in vivo, regardless of environmental changes, through properties inherent to the clock proteins. This included the activity of ATPase, an enzyme responsible for producing chemical energy, which allows cells to perform their duties in various processes.

“The activity of this protein, which acts as the pacemaker of the cyanobacterial clock, did not change in response to different environmental conditions. This property, which appears to be innate to the protein itself, is likely critical for preserving circadian timing despite environmental changes,” explains Kumiko Ito-Miwa, lead author, building on a concept originally proposed and long pursued by Takao Kondo.

The findings suggest that the environment inside cyanobacterial cells may fine-tune the circadian clock to align it with Earth’s 24-hour cycle, offering significant insight into the fundamental question of how living organisms measure time.

Rhythms of KaiC period mutants in cells and in vitro (representative examples).
Even when temperature or light intensity changes, the circadian period of the wild type (normal strain), as well as those of short- and long-period mutants, remains largely unchanged. Moreover, compared with the in vitro clock, the intracellular clock shifts slightly toward the Earth’s 24-hour cycle: short-period mutants lengthen slightly, whereas long-period mutants shorten slightly.

The article, “Intrinsic period stability of the cyanobacterial circadian oscillator
across in vitro and in vivo conditions,” was published in PNAS at DOI: https://doi.org/10.1073/pnas.2526714123

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Light-regulated enzymatic degradation and spatial patterning through localized irradiation

The article, “Light-Programmable Polyester Networks with Movable Cross-Links for On-Demand Enzymatic Degradation,” will be published in ACS Nano at DOI: https://doi.org/10.1021/acsnano.5c19646

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• Professor Takashima Yoshinori (Researcher Directory)

• Polymeric Materials Design Laboratory

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• ResOU（Research at Osaka University）website