今泉 研人 (イマイズミ ケント)

Imaizumi, Kent

写真a

所属(所属キャンパス)

医学部 生理学教室 (信濃町)

職名

特任助教(有期)

 

論文 【 表示 / 非表示

  • A non-invasive system to monitor in vivo neural graft activity after spinal cord injury.

    Ago K, Nagoshi N, Imaizumi K, Kitagawa T, Kawai M, Kajikawa K, Shibata R, Kamata Y, Kojima K, Shinozaki M, Kondo T, Iwano S, Miyawaki A, Ohtsuka M, Bito H, Kobayashi K, Shibata S, Shindo T, Kohyama J, Matsumoto M, Nakamura M, Okano H

    Communications biology 5 ( 1 ) 803 2022年08月

  • Pathogenic Mutation of TDP-43 Impairs RNA Processing in a Cell Type-Specific Manner: Implications for the Pathogenesis of ALS/FTLD

    Imaizumi K., Ideno H., Sato T., Morimoto S., Okano H.

    eNeuro (eNeuro)  9 ( 3 )  2022年05月

     概要を見る

    Transactivating response element DNA-binding protein of 43 kDa (TDP-43), which is encoded by the TARDBP gene, is an RNA-binding protein with fundamental RNA processing activities, and its loss-of-function (LOF) has a central role in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). TARDBP mutations are postulated to inactivate TDP-43 functions, leading to impaired RNA proc-essing. However, it has not been fully examined how mutant TDP-43 affects global RNA regulation, especially in human cell models. Here, we examined global RNA processing in forebrain cortical neurons derived from human induced pluripotent stem cells (iPSCs) with a pathogenic TARDBP mutation encoding the TDP-43K263E protein. In neurons expressing mutant TDP-43, we detected disrupted RNA regulation, including global changes in gene ex-pression, missplicing, and aberrant polyadenylation, all of which were highly similar to those induced by TDP-43 knock-down. This mutation-induced TDP-43 LOF was not because of the cytoplasmic mislocalization of TDP-43. Intriguingly, in nonneuronal cells, including iPSCs and neural progenitor cells (NPCs), we did not observe impairments in RNA processing, thus indicating that the K263E mutation results in neuron-specific LOF of TDP-43. This study characterizes global RNA processing impairments induced by mutant TDP-43 and reveals the unprece-dented cell type specificity of TDP-43 LOF in ALS/FTLD pathogenesis.

  • Modulation by DREADD reveals the therapeutic effect of human iPSC-derived neuronal activity on functional recovery after spinal cord injury

    Kitagawa T., Nagoshi N., Kamata Y., Kawai M., Ago K., Kajikawa K., Shibata R., Sato Y., Imaizumi K., Shindo T., Shinozaki M., Kohyama J., Shibata S., Matsumoto M., Nakamura M., Okano H.

    Stem Cell Reports (Stem Cell Reports)  17 ( 1 ) 127 - 142 2022年01月

    ISSN  22136711

     概要を見る

    Transplantation of neural stem/progenitor cells (NS/PCs) derived from human induced pluripotent stem cells (hiPSCs) is considered to be a promising therapy for spinal cord injury (SCI) and will soon be translated to the clinical phase. However, how grafted neuronal activity influences functional recovery has not been fully elucidated. Here, we show the locomotor functional changes caused by inhibiting the neuronal activity of grafted cells using a designer receptor exclusively activated by designer drugs (DREADD). In vitro analyses of inhibitory DREADD (hM4Di)-expressing cells demonstrated the precise inhibition of neuronal activity via administration of clozapine N-oxide. This inhibition led to a significant decrease in locomotor function in SCI mice with cell transplantation, which was exclusively observed following the maturation of grafted neurons. Furthermore, trans-synaptic tracing revealed the integration of graft neurons into the host motor circuitry. These results highlight the significance of engrafting functionally competent neurons by hiPSC-NS/PC transplantation for sufficient recovery from SCI.

  • Long-term selective stimulation of transplanted neural stem/progenitor cells for spinal cord injury improves locomotor function.

    Kawai M, Imaizumi K, Ishikawa M, Shibata S, Shinozaki M, Shibata T, Hashimoto S, Kitagawa T, Ago K, Kajikawa K, Shibata R, Kamata Y, Ushiba J, Koga K, Furue H, Matsumoto M, Nakamura M, Nagoshi N, Okano H

    Cell reports (Cell Reports)  37 ( 8 ) 110019 2021年11月

     概要を見る

    In cell transplantation therapy for spinal cord injury (SCI), grafted human induced pluripotent stem cell-derived neural stem/progenitor cells (hiPSC-NS/PCs) mainly differentiate into neurons, forming synapses in a process similar to neurodevelopment. In the developing nervous system, the activity of immature neurons has an important role in constructing and maintaining new synapses. Thus, we investigate how enhancing the activity of transplanted hiPSC-NS/PCs affects both the transplanted cells themselves and the host tissue. We find that chemogenetic stimulation of hiPSC-derived neural cells enhances cell activity and neuron-to-neuron interactions in vitro. In a rodent model of SCI, consecutive and selective chemogenetic stimulation of transplanted hiPSC-NS/PCs also enhances the expression of synapse-related genes and proteins in surrounding host tissues and prevents atrophy of the injured spinal cord, thereby improving locomotor function. These findings provide a strategy for enhancing activity within the graft to improve the efficacy of cell transplantation therapy for SCI.

  • Non-viral Induction of Transgene-free iPSCs from Somatic Fibroblasts of Multiple Mammalian Species

    Yoshimatsu S., Nakajima M., Iguchi A., Sanosaka T., Sato T., Nakamura M., Nakajima R., Arai E., Ishikawa M., Imaizumi K., Watanabe H., Okahara J., Noce T., Takeda Y., Sasaki E., Behr R., Edamura K., Shiozawa S., Okano H.

    Stem Cell Reports (Stem Cell Reports)  16 ( 4 ) 754 - 770 2021年04月

    ISSN  22136711

     概要を見る

    Induced pluripotent stem cells (iPSCs) are capable of providing an unlimited source of cells from all three germ layers and germ cells. The derivation and usage of iPSCs from various animal models may facilitate stem cell-based therapy, gene-modified animal production, and evolutionary studies assessing interspecies differences. However, there is a lack of species-wide methods for deriving iPSCs, in particular by means of non-viral and non-transgene-integrating (NTI) approaches. Here, we demonstrate the iPSC derivation from somatic fibroblasts of multiple mammalian species from three different taxonomic orders, including the common marmoset (Callithrix jacchus) in Primates, the dog (Canis lupus familiaris) in Carnivora, and the pig (Sus scrofa) in Cetartiodactyla, by combinatorial usage of chemical compounds and NTI episomal vectors. Interestingly, the fibroblasts temporarily acquired a neural stem cell-like state during the reprogramming. Collectively, our method, robustly applicable to various species, holds a great potential for facilitating stem cell-based research using various animals in Mammalia.

全件表示 >>

KOARA(リポジトリ)収録論文等 【 表示 / 非表示

競争的研究費の研究課題 【 表示 / 非表示

  • 臓器形成における自発的対称性の破れをオルガノイドモデルで明らかにする

    2021年04月
    -
    2023年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 今泉 研人, 新学術領域研究(研究領域提案型), 補助金,  研究代表者

  • 領域特異的なiPS細胞由来神経幹細胞を用いた脊髄損傷に対する新しい再生医療の開発

    2019年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 今泉 研人, 若手研究, 補助金,  研究代表者