News and Publications


New Publication

Published:
24 Sep 2021

A common genetic variant of a mitochondrial RNA processing enzyme predisposes to insulin resistance

CRISPR-Cas9 genome editing was used to introduce the missense N437S variant into the mouse Mrpp3 gene to study the causes of insulin resistance on a high-fat diet. The variant did not influence mitochondrial gene expression markedly, but instead, it reduced mitochondrial calcium that lowered insulin release from the pancreatic islet β cells of the Mrpp3 variant mice. Reduced insulin secretion resulted in lower insulin levels that contributed to imbalanced metabolism and liver steatosis.

The findings revealed that the MRPP3 variant may be a predisposing factor to insulin resistance and metabolic disease in the human population.


Science Advances - 24 Sep 2021 • Vol 7, Issue 39 •
    doi/10.1126/sciadv.abi7514

New Publication

Published:
23 Feb 2021

Generation of reconstituted hemato-lymphoid murine embryos by placental transplantation into embryos lacking HSCs



In order to increase the contribution of donor HSC cells, irradiation and DNA alkylating agents have been commonly used as experimental methods to eliminate HSCs for adult mice. But a technique of HSC deletion for mouse embryo for increase contribution of donor cells has not been published. Here, we established for the first time a procedure for placental HSC transplantation into E11.5 Runx1-deficient mice mated with G1-HRD-Runx1 transgenic mice (Runx1-/-::Tg mice) that have no HSCs in the fetal liver. Following the transplantation of fetal liver cells from mice (allogeneic) or rats (xenogeneic), high donor cell chimerism was observed in Runx1-/-::Tg embryos. Furthermore, chimerism analysis and colony assay data showed that donor fetal liver hematopoietic cells contributed to both white blood cells and red blood cells. Moreover, secondary transplantation into adult recipient mice indicated that the HSCs in rescued Runx1-/-::Tg embryos had normal abilities. These results suggest that mice lacking fetal liver HSCs are a powerful tool for hematopoiesis reconstruction during the embryonic stage and can potentially be used in basic research on HSCs or xenograft models. (Read More –> )



Published in Scientific Reports 11, Article number: 4374 (2021)

Research Outline (PDF In Japanese language)

New Publication

Published:
3 Feb 2021

DHODH inhibition synergizes with DNA-demethylating agents in the treatment of myelodysplastic syndromes

Key Points

• DHODH inhibition synergizes with DNA-demethylating agents in the treatment of MDS.
• DHODH inhibition enhances the incorporation of decitabine into DNA in MDS cells.


Blood Advances - Issue: Blood Adv(2021) 5 (2): 438–450
    https://doi.org/10.1182/bloodadvances.2020001461

New Publication

Published:
20 Jan 2021

Environment-based object values learned by local network in the striatum tail



Value and reward are known to be encoded in the part of the brain called the basal ganglia. Research has identified the specific neuronal circuits underlying environment-based value learning.

Obtaining valuables is one of the most important actions for the survival of animals, including humans. And even if they are the same, their value to animals changes depending on the environment and circumstances in which they are placed. Animals make good judgments about their value based on experience and learning. So what is the mechanism by which we learn the value of things?


Published in PNAS January 26, 2021 118 (4) e2013623118

Tsukuba Journal - University of Tsukuba

Research Outline (PDF In Japanese language)

New Publication

Published:
6 Jan 2021

Environment-based object values learned by local network in the striatum tail


In skeletal muscle, quiescent satellite cells maintain low levels of protein synthesis, mediated in part through the phosphorylation of eIF2α (P-eIF2α). Paradoxically, P-eIF2α also increases the translation of specific mRNAs, which is mediated by P-eIF2α dependent read through of inhibitory upstream open reading frames (uORFs). Here, we ask whether P-eIF2α dependent mRNA translation enables expansion of satellite cells. We demonstrate that uORFs in the 5’UTR of mRNA for the mitotic spindle stability gene Tacc3 direct P-eIF2α dependent translation. Satellite cells deficient for TACC3 exhibit defects in expansion, self-renewal and regeneration of skeletal muscle.

Satellite cell expansion is mediated by P-eIF2α-dependent Tacc3 translation
Development DOI: 10.1242/dev.194480

Tsukuba Journal - University of Tsukuba (Japanese language)

Research Outline (PDF In Japanese language)

New Publication

Published:
25 Nov 2020

Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.



Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide current understanding of fundamental molecular changes that occur during space travel.

Cell – Volume 183, Issue 5, 25 November 2020, Pages 1162-1184

New Publication

Published:
11 Dec 2020

Generation of KS-58 as the first K-Ras(G12D)-inhibitory peptide presenting anti-cancer activity in vivo.



In vitro data and molecular dynamics simulations suggest that KS-58 enters cells and blocks intracellular Ras–effector protein interactions. KS-58 selectively binds to K-Ras(G12D) and suppresses the in vitro proliferation of the human lung cancer cell line A427 and the human pancreatic cancer cell line PANC-1, both of which express K-Ras(G12D). Moreover, KS-58 exhibits anti-cancer activity when given as an intravenous injection to mice with subcutaneous or orthotropic PANC-1 cell xenografts. The anti-cancer activity is further improved by combination with gemcitabine.

Scientific Reports – 10, Article number: 21671 (2020)

New Publication

Published:
26 Nov 2020

A New Era for Space Life Science: International Standards for Space Omics Processing

(Published Nov 26, 2020)



TMRC Genomics Division members have been involved in the formation of ISSOP (International Standards for Space Omics Processing).

Scientists across the world are conducting space omics studies to develop countermeasures for safe and effective crewed space missions. However, optimal extraction of scientific insight from such data is contingent on improved standardization.

ISSOP has been founded as an international consortium of scientists who aim to enhance guidelines between space biologists globally.

This paper informs scientists and data scientists from many fields about the challenges and future avenues of space omics and can serve as an introductory reference for new members in the space biology discipline.

A New Era for Space Life Science: International Standards for Space Omics Processing
Patterns - November 25, 2020


Press Release - University of Tsukuba Website (in Japanese language)
Research Outline PDF (In Japanese language)

New Publication

Published:
11 Nov 2020

From Pleasure to Decision-Making. Getting Closer to Understanding the Diverse and Complex Functions of Dopamine Neurons.

(Published Nov 11, 2020)

Professor Masayuki Matsumoto, TMRC University of Tsukuba, Faculty of Medicine



“Every day of our lives, we make many different decisions. In many cases, we are faced with choosing which of several options would be most rewarding for us. What kind of brain mechanisms might be responsible for the logical decision-making that helps us choose more rewarding behaviors? The key to answering this question is a substance called dopamine, and the neurons that produce it, called dopamine neurons. Prof. Matsumoto is studying the functions of dopamine neurons with the aim of uncovering what role they play in decision-making.”

Read More →
(Article by Science Communicator at the Office of Public Relations, University of Tsukuba)


Read More → Professor Masayuki Matsumoto at TMRC

New Publication

Published:
11 Nov 2020

Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice

(Published Nov 11, 2020)


The intestinal environment, including the gut flora, has been shown to interact with brain function.

In this study, the relationship between the intestinal flora and sleep was investigated using mice in which the intestinal flora was removed by chronic antibiotic administration. A metabolome analysis of the contents of the cecum determined that the state of intestinal metabolism in “intestinal flora-removed” mice showed significant changes in the metabolic pathways of amino acids involved in neurotransmitter synthesis compared to normal mice. In particular, vitamin B6 was significantly reduced and serotonin, which regulates nerve function, was depleted.

On the other hand, a significant increase in glycine and gamma-aminobutyric acid (GABA), which suppress the activity of nerve cells, was observed.



When sleep was analyzed using EEG and EMG, “intestinal flora-removed” mice had decreased sleep in the light period (sleep period) and increased sleep in the dark period (active period). The day and night, sleep / wakefulness pattern was weakened. It was also found that theta waves, which are the characteristic brain waves components of REM sleep with cerebral cortex activity, were reduced. These findings suggest that removal of the gut flora may reduce sleep quality.

It is expected that further research may allow new methodologies for promoting improved health through a deeper understanding of the interaction between the intestinal environment and brain function (gut-brain axis) and eating habits.

Gut microbiota depletion by chronic antibiotic treatment alters the sleep/wake architecture and sleep EEG power spectra in mice
Scientific Reports - 10, Article number: 19554 (2020)
doi: 10.1038/s41598-020-76562-9

Research Outline PDF (In Japanese language)