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MORI Tatsufumi

    Life Science Research Institute　Research assistant
Last Updated :2024/04/25

Researcher Information

J-Global ID

Research Interests

  • MSC   再生医療   多能性幹細胞   体外培養   発生工学   卵成熟   顕微授精   胚発生   卵胞培養   

Research Areas

  • Life sciences / Orthopedics / MSC
  • Life sciences / Developmental biology

Academic & Professional Experience

  • 2015/04 - 2018  Kindai UniversityLife Science Research Institute助手

Association Memberships

  • the Japanese Society of Cartilage Metabolism   THE JAPANESE SOCIETY FOR REGENERATIVE MEDICINE   JAPAN SOCIETY FOR REPRODUCTIVE MEDICINE   Japanese Society of Mammalian Ova Research   JAPAN SOCIETY OF FERTILIZATION AND IMPLANTATION   

Published Papers

  • Kensuke Toriumi; Yuta Onodera; Toshiyuki Takehara; Tatsufumi Mori; Joe Hasei; Kanae Shigi; Natsumi Iwawaki; Toshifumi Ozaki; Masao Akagi; Mahito Nakanishi; Takeshi Teramura
    iScience 26 (7) 106946 - 106946 2023/07 
    Mesenchymal stem cells (MSCs) are used as a major source for cell therapy, and its application is expanding in various diseases. On the other hand, reliable method to evaluate quality and therapeutic properties of MSC is limited. In this study, we focused on TWIST1 that is a transcription factor regulating stemness of MSCs and found that the transmembrane protein LRRC15 tightly correlated with the expression of TWIST1 and useful to expect TWIST1-regulated stemness of MSCs. The LRRC15-positive MSC populations in human and mouse bone marrow tissues highly expressed stemness-associated transcription factors and therapeutic cytokines, and showed better therapeutic effect in bleomycin-induced pulmonary fibrosis model mice. This study provides evidence for the important role of TWIST1 in the MSC stemness, and for the utility of the LRRC15 protein as a marker to estimate stem cell quality in MSCs before cell transplantation.
  • Tatsufumi Mori; Masatsugu Igarashi; Yuta Onodera; Toshiyuki Takehara; Maki Itokazu; Takeshi Teramura
    Biochemical and Biophysical Research Communications 2023/04
  • Maki Itokazu; Yuta Onodera; Tatsufumi Mori; Shinji Inoue; Kotaro Yamagishi; Akihiro Moritake; Natsumi Iwawaki; Kanae Shigi; Toshiyuki Takehara; Yuji Higashimoto; Masao Akagi; Takeshi Teramura
    The Journal of biological chemistry 298 (7) 102098 - 102098 2022/07 
    Sarcopenia is an aging-associated attenuation of muscular volume and strength and is the major cause of frailty and falls in elderly individuals. The number of individuals with sarcopenia is rapidly increasing worldwide; however, little is known about the underlying mechanisms of the disease. Sarcopenia often copresents with obesity, and some patients with sarcopenia exhibit accumulation of peri-organ or intra-organ adipose tissue as ectopic fat deposition, including atrophied skeletal muscle. In this study, we showed that transplantation of the perimuscular adipose tissue (PMAT) to the hindlimb thigh muscles of young mice decreased the number of integrin α7/CD29-double positive muscular stem/progenitor cells and that the reaction was mediated by PMAT-derived exosomes. We also found that the inhibition of cell proliferation was induced by Let-7d-3p miRNA that targets HMGA2, which is an important transcription factor for stem cell self-renewal, in muscular stem/progenitor cells and the composite molecular reaction in aged adipocytes. Reduction of Let-7 miRNA repressor Lin28 A/B and activation of nuclear factor-kappa B signaling can lead to the accumulation of Let-7d-3p in the exosomes of aged PMAT. These findings suggest a novel crosstalk between adipose tissue and skeletal muscle in the development of aging-associated muscular atrophy and indicate that adipose tissue-derived miRNAs may play a key role in sarcopenia.
  • Tatsufumi Mori; Yuta Onodera; Maki Itokazu; Toshiyuki Takehara; Kanae Shigi; Natsumi Iwawaki; Masao Akagi; Takeshi Teramura
    Mechanisms of ageing and development 201 111619 - 111619 2022/01 
    Frailty of the locomotory organs has become a widespread problem in the geriatric population. The major factor leading to frailty is an age-associated decrease in muscular mass and a reduced number of muscular cells and myofibers. In aged muscular tissues, muscular satellite cells (MuSCs) are reduced due to abnormalities in their self-renewal and the induction of apoptosis. However, the molecular mechanisms connecting aging-associated physiological changes and the reduction of MuSCs are largely unknown. NIMA-related kinase 2 (Nek2), a member of the Nek family of serine/threonine kinases, was found to be downregulated in aged MuSCs/progenitors. Further, Nek2 downregulation was found to inhibit self-renewal and apoptotic cell death by activating the p53-dependent checkpoint. Attenuated NEK2 expression was also observed in the muscular tissues of elderly donors, and its function was confirmed to be conserved in humans. Overall, this study proposes a novel mechanism for inducing muscular atrophy to understand aging-associated muscular diseases.
  • Takatoshi Tsujimoto; Tatsufumi Mori; Kei Houri; Yuta Onodera; Toshiyuki Takehara; Kanae Shigi; Shinichi Nakao; Takeshi Teramura; Kanji Fukuda
    Biochem Biophys Res Commun 523 (3) 707 - 712 2020/03 [Refereed]
     
    Removal of dysfunctional mitochondria is essential step to maintain normal cell physiology, and selective autophagy in mitochondria, called mitophagy, plays a critical role in quality control of mitochondria. While in several diseases and aging, disturbed mitophagy has been observed. In stem cells, accumulation of damaged mitochondria can lead to deterioration of stem cell properties. Here, we focused on miR-155-5p (miR-155), one of the most prominent miRNAs in inflammatory and aged tissues, and found that miR-155 disturbed mitophagy in mesenchymal stem cells (MSCs). As a molecular mechanism of miR-155-mediated mitophagy suppression, we found that BCL2 associated athanogene 5 (BAG5) is a direct target of miR-155. Reduction of BAG5 resulted in destabilization of PTEN-induced kinase (PINK1) and consequently disrupted mitophagy. Our study suggests a novel mechanism connecting aging and aging-associated inflammation with mitochondrial dysfunction in stem cells through a miRNA-mediated mechanism.
  • miR-142 induces accumulation of reactive oxygen species (ROS) by inhibiting pexophagy in aged bone marrow mesenchymal stem cells.
    Kei Houri; Tatsufumi Mori; Yuta Onodera; Takatoshi Tsujimoto; Toshiyuki Takehara; Shinichi Nakao; Takeshi Teramura; kanji Fukuda
    Sicentific Report 2020/02 [Refereed]
  • Teramura T; Matsuda K; Takehara T; Shinohara K; Miyashita Y; Mieno Y; Mori T; Fukuda K; Suzuki K; Suemori H
    Biochemical and biophysical research communications 503 (4) 3114 - 3120 0006-291X 2018/09 [Refereed]
  • Onodera Y; Teramura T; Takehara T; Itokazu M; Mori T; Fukuda K
    PloS one 13 (10) e0204860  2018 [Refereed]
  • Yuta Onodera; Takeshi Teramura; Toshiyuki Takehara; Kayoko Obora; Tatsufumi Mori; Kanji Fukuda
    Aging Cell Blackwell Publishing Ltd 16 (6) 1369 - 1380 1474-9726 2017/12 [Refereed]
     
    Inflammation-induced reactive oxygen species (ROS) are implicated in cellular dysfunction and an important trigger for aging- or disease-related tissue degeneration. Inflammation-induced ROS in stem cells lead to deterioration of their properties, altering tissue renewal or regeneration. Pathological ROS generation can be induced by multiple steps, and dysfunction of antioxidant systems is a major cause. The identification of the central molecule mediating the above-mentioned processes would pave the way for the development of novel therapeutics for aging, aging-related diseases, or stem cell therapies. In recent years, microRNAs (miRNAs) have been shown to play important roles in many biological reactions, including inflammation and stem cell functions. In inflammatory conditions, certain miRNAs are highly expressed and mediate some cytotoxic actions. Here, we focused on miR-155, which is one of the most prominent miRNAs in inflammation and hypothesized that miR-155 participates to inflammation-induced ROS generation in stem cells. We observed mesenchymal stem cells (MSCs) from 1.5-year-old aged mice and determined that antioxidants, Nfe2l2, Sod1, and Hmox1, were suppressed, while miR-155-5p was highly expressed. Subsequent in vitro studies demonstrated that miR-155-5p induces ROS generation by suppression of the antioxidant genes by targeting the common transcription factor C/ebpβ. Moreover, this mechanism occurred during the cell transplantation process, in which ROS generation is triggering loss of transplanted stem cells. Finally, attenuation of antioxidants and ROS accumulation were partially prevented in miR-155 knockout MSCs. In conclusion, our study suggests that miR-155 is an important mediator connecting aging, inflammation, and ROS generation in stem cells.
  • Yuta Onodera; Takeshi Teramura; Toshiyuki Takehara; Kayoko Obora; Tatsufumi Mori; Kanji Fukuda
    AGING CELL WILEY 16 (6) 1369 - 1380 1474-9726 2017/12 [Refereed]
     
    Inflammation-induced reactive oxygen species (ROS) are implicated in cellular dysfunction and an important trigger for aging- or disease-related tissue degeneration. Inflammation-induced ROS in stem cells lead to deterioration of their properties, altering tissue renewal or regeneration. Pathological ROS generation can be induced by multiple steps, and dysfunction of antioxidant systems is a major cause. The identification of the central molecule mediating the above-mentioned processes would pave the way for the development of novel therapeutics for aging, aging-related diseases, or stem cell therapies. In recent years, microRNAs (miRNAs) have been shown to play important roles in many biological reactions, including inflammation and stem cell functions. In inflammatory conditions, certain miRNAs are highly expressed and mediate some cytotoxic actions. Here, we focused on miR-155, which is one of the most prominent miRNAs in inflammation and hypothesized that miR-155 participates to inflammation-induced ROS generation in stem cells. We observed mesenchymal stem cells (MSCs) from 1.5-year-old aged mice and determined that antioxidants, Nfe2l2, Sod1, and Hmox1, were suppressed, while miR-155-5p was highly expressed. Subsequent in vitro studies demonstrated that miR-155-5p induces ROS generation by suppression of the antioxidant genes by targeting the common transcription factor C/ebp beta Moreover, this mechanism occurred during the cell transplantation process, in which ROS generation is triggering loss of transplanted stem cells. Finally, attenuation of antioxidants and ROS accumulation were partially prevented in miR-155 knockout MSCs. In conclusion, our study suggests that miR-155 is an important mediator connecting aging, inflammation, and ROS generation in stem cells.
  • Takao Inoue; Kumiko Takemori; Nobuyuki Mizuguchi; Masatomo Kimura; Takaaki Chikugo; Man Hagiyama; Azusa Yoneshige; Tatsufumi Mori; Osamu Maenishi; Takashi Kometani; Tatsuki Itoh; Takao Satou; Akihiko Ito
    Experimental physiology 102 (11) 1435 - 1447 0958-0670 2017/11 [Refereed]
     
    NEW FINDINGS: What is the central question of this study? An inverse correlation between circulating adiponectin and many diseases has been reported, but some studies have found no correlation. To evaluate this controversy, we investigated the relationship between heart-bound adiponectin and hypertension or cardiac hypertrophy, compared with serum adiponectin. What is the main finding and its importance? Using hypertensive and normotensive rats, we found that heart-bound adiponectin was inversely correlated with cardiac hypertrophy, suggesting that heart-bound adiponectin has a more important function in preventing cardiac hypertrophy than circulating adiponectin. Our study provides new insights regarding the role of adiponectin in diseases. The inverse correlation between circulating adiponectin concentration and hypertension or cardiac hypertrophy is still controversial. In addition to circulating adiponectin, adiponectin is also bound to tissues such as the heart and skeletal muscle. In this study, we investigated the relationship of serum adiponectin and heart-bound adiponectin with hypertension and cardiac hypertrophy. Four types of hypertensive rats presenting different blood pressure levels were used at different ages, as follows: normotensive Wistar-Kyoto rats (WKYs); two sub-strains (strains C and B2, having low and high blood pressure, respectively) of spontaneously hypertensive rats (SHRs); and stroke-prone SHRs (SHRSPs). Blood pressure, heart-to-body weight ratio, serum adiponectin and heart-bound adiponectin were determined. Histopathological analysis of the heart was carried out to evaluate the relationship with heart-bound adiponectin. Serum adiponectin concentration was not inversely correlated with blood pressure or heart-to-body weight ratio. In contrast, heart-bound adiponectin levels were significantly lower in SHRSPs than in other strains at respective ages. This resulted from a decrease in T-cadherin expression, which induced adiponectin binding to tissues. No significant difference in heart-bound adiponectin among WKYs and SHRs (C and B2) was detected, indicating that heart-bound adiponectin is not related to hypertension. In addition, differences in heart-bound adiponectin did not affect AMP-activated protein kinase in the traditional adiponectin activation cascade. Histopathological analysis revealed that heart-bound adiponectin was inversely correlated with cardiomyocyte hypertrophy and left ventricular wall thickness and, in part, with cardiac fibrosis. These results suggest that the decreased level of heart-bound adiponectin in SHRSPs is more related to their cardiac hypertrophy than circulating adiponectin.
  • Inoue Takao; Takemori Kumiko; Muzuguchi Nobuyuki; Kimura Masatomo; Chikugo Takaaki; Hagiyama Man; Yoneshige Azusa; Mori Tatsufumi; Kometani Takashi; Itoh Tatsuki; Satou Takao; Ito Akihiko
    JOURNAL OF HYPERTENSION LIPPINCOTT WILLIAMS & WILKINS 34 E288 - E288 0263-6352 2016/09 [Refereed]
  • Hiroki Izumi; Yuki Miyamoto; Tatsufumi Mori; Yuka Hashigami; Yasutaka Chiba; Takeshi Teramura; Shu Hashimoto; Kanji Fukuda; Yoshiharu Morimoto; Yoshihiko Hosoi
    Reproductive Medicine and Biology John Wiley and Sons Ltd 12 (4) 179 - 185 1447-0578 2013 [Refereed]
     
    Purpose: Current approaches to in vitro maturation (IVM) may result in low efficiency and inadequate quality of the oocytes due to insufficient cytoplasmic maturation. Although positive effects of the cysteamine supplementation in IVM medium for oocyte nuclear maturation or male pronuclear formation have been confirmed, it is still controversial whether the cysteamine addition affects embryo development after IVM. We aimed here to confirm the effect of cysteamine addition into IVM medium for subsequent embryo development in vitro. Methods: We administered the cysteamine to the IVM culture of rabbit immature oocytes at various concentrations and observed the developmental rate, speed to reach blastocyst stage and cell numbers at the blastocyst stage. Results: Cysteamine supplementation improved developmental rate to blastocyst stage of the IVM oocytes. On the other hand, addition of glutathione (GSH) inhibitor buthionine sulfoximine inhibited GSH accumulation in the oocytes and subsequent embryo development to the blastocyst stage. Conclusions: Controlling the GSH quantity of IVM oocytes may be an important factor for success of embryo development, and it is quite probable that a cysteamine supplementation can contribute to an increase of GSH content in oocyte. © 2013 Japan Society for Reproductive Medicine.

Conference Activities & Talks

  • フィブリノーゲンは培養機材上へのbasic-FGFの安定化を誘導し、血清低減環境下での 間葉系幹細胞の増殖促進に寄与する
    第22回日本再生医療学会総会
  • NINA-related kinase (Nek2) は加齢マウスでの筋衛星細胞の減少に関与する
    第37回日本整形外科学会基礎学術集会
  • NINA-related kinase (NEK2)は加齢マウスでの筋衛星細胞の減少に関与する
    第21回日本再生医療学会総会
  • 間葉系幹細胞のステムネスにおけるTWIST1の機能解明
    第19回 日本再生医療学会総会
  • TAK1 regulates proliferation of BMMSCs through activation of Yes-associated protein (Yap1)
    第32回 日本軟骨代謝学会
  • Nanog制御性マイクロRNAによるミトコンドリア複製制御と幹細胞の形質変化について  [Not invited]
    森 樹史
    第17回再生医療学会総会
  • 多能性関連転写因子NanogはmiR19bによるTfamの抑制を介してミトコンドリアの制御に関与する  [Not invited]
    森 樹史
    第31回日本軟骨代謝学会

MISC

Research Grants & Projects

  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2021/04 -2024/03 
    Author : 森 樹史; 寺村 岳士; 竹原 俊幸
     
    間葉系幹細胞(Mesenchymal stem cell : MSC、stromal stem cell)は骨髄や脂肪などから分離される組織幹細胞であり、優れたサイトカイン産生能力と分化能を有する事から様々な疾患に対する再生医療材料としての期待が高まっている。一方で、多能性幹細胞とは異なり、ドナー年齢や細胞の継代数などにより劣化しやすく、維持・供給が安定しないという課題がある。また、品質を評価するマーカーが存在しないため、供給された細胞の品質がばらつくという問題も抱えている。申請者らは、転写因子Twist1がMSCの幹細胞性に極めて重要な分子であり、MSCの性能を評価する上で有用であることを発見している。体内において、MSCは骨髄、脂肪組織、筋組織等の血管周囲や間質に見られる。体外培養時と同様、体内においてもMSCは加齢や炎症などストレスの影響を受けるため、若齢患者から得られるMSCと高齢患者から得られるMSCでは性質、品質が全く異なることがわかってきている。一方で、体内に存在するMSCは、存在場所、ストレス蓄積量、それまでの分裂回数など複数の要素によってその品質が非常にヘテロな状態になっており、たとえ高齢ドナーであっても適した細胞マーカーに基づき評価分別できれば、より高い治療効果を安定的に得られると考えられる。本研究では、同知見を有用な医療技術として発展させる為、Twist1を操作しヒトMSCの作製・評価を目的として行う。
  • Japan Society for the Promotion of Science：Grants-in-Aid for Scientific Research
    Date (from‐to) : 2019/04 -2021/03 
    Author : MORI Tatsufumi
     
    MSCs are somatic stem cells can isolated from various connective tissues such as bone marrow, fat, and synovial membrane. Because of its properties of cytokine secretion, multiple differentiation and niche formation, MSCs has been an attractive cell source for cell transplantation therapy. On the other hand, molecular mechanisms regulating stemness of the MSCs is largely unknown. Here we focused on a transcription factor TWIST1 as a molecule involving stemness of the MSCs. In the human MSCs, overexpression of TWIST1 significantly activated cell proliferation and inhibited differentiation, contrary, suppression of TWIST1 resulted in reduction of cell proliferation. Transcriptome and ChIPseq analysis revealed that TWIST1 directly bind to promoter region of other transcription factors regulating undifferentiation status of the stem cells. From these we concluded that TWIST1 is a master regulator of stemness in the MSCs and useful as a marker evaluating potentials of the MSCs.

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