Rejuvenation of human mesenchymal stem cells using a nonintegrative and conditionally removable Sendai virus vector.

Oshimura M, Tabata T, Uno N, Takata S, Hichiwa G, Kanazawa I, Endo T, Honma K, Wang Y, Kazuki K, Tu H, Iida Y, Abe S, Kazuki Y.

Sci Rep. 2024 Oct 9;14(1):23623.

Developing a workflow for the isolation of hybridoma cells producing fully human antigen-specific antibodies using a surface IgG detection method.

Satofuka H, Wang Y, Tanaka H, Hiramatsu K, Morimoto K, Takayama H, Tu H, Qiao Y, Ito S, Gao X, Oshimura M, Kazuki Y.

Sci Rep. 2024 Oct 4;14(1):23138.

Characterization of immortalized ovarian epithelial cells with BRCA1/2 mutation.

Komatsu H, Okawa M, Kazuki Y, Kazuki K, Hichiwa G, Shimoya K, Sato S, Taniguchi F, Oshimura M, Harada T.

Hum Cell. 2024 Jul;37(4):986-996. 

Rapid human genomic DNA cloning into mouse artificial chromosome via direct chromosome transfer from human iPSC and CRISPR/Cas9-mediated translocation

Hitomaru Miyamoto, Hiroaki Kobayashi, Nanami Kishima, Kyotaro Yamazaki, Shusei Hamamichi, Narumi Uno, Satoshi Abe, Yosuke Hiramuki, Kanako Kazuki, Kazuma Tomizuka, Yasuhiro Kazuki

Nucleic Acids Research, 2024, 1–14

Neocortical neuronal production and maturation defects in the TcMAC21 mouse model of Down syndrome

Kurabayashi N, Fujii K, Otobe Y, Hiroki S, Hiratsuka M, Yoshitane H, Kazuki Y, Takao K.

iScience. 2023 Nov 2;26(12):108379. 

Phenotypic features of dystrophin gene knockout pigs harboring a human artificial chromosome containing the entire dystrophin (DMD) gene 

Watanabe M, Miyamoto H, Okamoto K, Nakano K, Matsunari H, Kazuki K, Hasegawa K, Uchikura A, Takayanagi S, Umeyama K, Hiramuki Y, Kemter E, Klymuik N, Kurome M, Kessler B, Wolf E, Kazuki Y, Nagashima H.

Molecular therapy nucleic acids, 2023 Jul 23;33:444-453. 

Treatment of CHO cells with Taxol and reversine improves micronucleation and microcell-mediated chromosome transfer efficiency.

Uno N, Satofuka H, Miyamoto H, Honma K, Suzuki T, Yamazaki K, Ito R, Moriwaki T, Hamamichi S, Tomizuka K, Oshimura M, Kazuki Y.

Mol Ther Nucleic Acids. 2023 Jul 15;33:391-403. 

Human artificial chromosome carrying 3p21.3-p22.2 region suppresses hTERT transcription in oral cancer cells.

Ohira T, Yoshimura K, Kugoh H.

Chromosome Res. 2023 Jun 24;31(3):17.

Co-treatment of CHO cells with Taxol and reversine improves micronucleation and microcell-mediated chromosome transfer efficiency

Narumi Uno, Hiroyuki Satofuka, Hitomaru Miyamoto, Kazuma Tomizuka, Mitsuo Oshimura, Yasuhiro Kazuki.

Molecular therapy nucleic acids, July 14, 2023

Increased propensity for infantile spasms and altered neocortical excitation-inhibition balance in a mouse model of down syndrome carrying human chromosome 21.

Shao LR, Gao F, Chinnasamy V, Kazuki Y, Oshimura M, Reeves RH, Stafstrom CE.

Neurobiol Dis. 2023 Jun 13;184:106198. 

Hypermetabolism in mice carrying a near-complete human chromosome 21.

Sarver DC, Xu C, Rodriguez S, Aja S, Jaffe AE, Gao FJ, Delannoy M, Periasamy M, Kazuki Y, Oshimura M, Reeves RH, Wong GW.

Elife. 2023 May 30;12:e86023. 

Overexpression screen of chromosome 21 genes reveals modulators of Sonic hedgehog signaling relevant to Down syndrome.

Moyer AJ, Fernandez FX, Li Y, Klinedinst DK, Florea LD, Kazuki Y, Oshimura M, Reeves RH.

Dis Model Mech. 2023 Apr 1;16(4):dmm049712. 

Full-length human dystrophin on human artificial chromosome compensates for mouse dystrophin deficiency in a Duchenne muscular dystrophy mouse model.

Hiramuki Y, Abe S, Uno N, Kazuki K, Takata S, Miyamoto H, Takayama H, Morimoto K, Takehara S, Osaki M, Tanihata J, Takeda S, Tomizuka K, Oshimura M, Kazuki Y.

Scientific Reports. 2023 Mar 16;13(1):4360.

Efficient human-like antibody repertoire and hybridoma production in trans-chromosomic mice carrying megabase-sized human immunoglobulin loci.

Satofuka H, Abe S, Moriwaki T, Okada A, Kazuki K, Tanaka H, Yamazaki K, Hichiwa G, Morimoto K, Takayama H, Nakayama Y, Hatano S, Yada Y, Murakami Y, Baba Y, Oshimura M, Tomizuka K, Kazuki Y.

Nat Commun. 2022 Apr 5;13(1):1841. 

Panel of human cell lines with human/mouse artificial chromosomes.

Uno N, Takata S, Komoto S, Miyamoto H, Nakayama Y, Osaki M, Mayuzumi R, Miyazaki N, Hando C, Abe S, Sakuma T, Yamamoto T, Suzuki T, Nakajima Y, Oshimura M, Tomizuka K, Kazuki Y.

Scientific Reports. 2022 Feb 22;12(1):3009.

Locus-specific induction of gene expression from heterochromatin loci during cellular senescence.

Tomimatsu K, Bihary D, Olan I, Parry AJ, Schoenfelder S, Chan ASL, Slater GStC, Ito Y, Rugg-Gunn PJ, Kirschner K, Bermejo-Rodriguez C, Seko T, Kugoh H, Shiraishi K, Sayama K, Kimura H, Fraser P, Narita M, Samarajiwa SA, Narita M. 

Nature Aging, 2, 31-45, 2022

Activation of PPARγ in bladder cancer via introduction of the long arm of human chromosome 9. Shimizu R, Ohira T, Yagyu T, Yumioka R, Yamaguchi N, Iwamoto H, Morizane S, Hilita K, Honda M, Takenaka A, Kugoh H.

Oncology Letters, 23, 92, 2022

Establishment of an antibody specific for AMIGO2 improves immunohistochemical evaluation of liver metastases and clinical outcomes in patients with colorectal cancer.

Goto K, Osaki M, Izutsu R, Tanaka H, Sasaki R, Tanio A, Satofuka H, Kazuki Y, Yamamoto M, Kugoh H, Ito H, Oshimura M, Fujiwara Y, Okada F. 

Diagnostic Pathology, 17, 16, 2022

A transchromosomic rat model with human chromosome 21 shows robust Down syndrome features.

Kazuki Y, Gao FJ, Yamakawa M, Hirabayashi M, Kazuki K, Kajitani N, Miyagawa-Tomita S, Abe S, Sanbo M, Hara H, Kuniishi H, Ichisaka S, Hata Y, Koshima M, Takayama H, Takehara S, Nakayama Y, Hiratsuka M, Iida Y, Matsukura S, Noda N, Li Y, Moyer AJ, Cheng B, Singh N, Richtsmeier JT, Oshimura M, Reeves RH. 

Am J Hum Genet. 2022 Jan 20:S0002-9297(21)00470-5. doi:10.1016/j.ajhg.2021.12.015.

MTA1, a metastasis‑associated protein, in endothelial cells is an essential molecule for angiogenesis.

Ishikawa M, Osaki M, Uno N, Ohira T, Kugoh H, Okada F.

Mol Med Rep. 2022 Jan;25(1):11. doi: 10.3892/mmr.2021.12527. Epub 2021 Nov 15.

Construction of stable mouse artificial chromosome from native mouse chromosome 10 for generation of transchromosomic mice.

Abe S, Honma K, Okada A, Kazuki K, Tanaka H, Endo T, Morimoto K, Moriwaki T, Hamamichi S, Nakayama Y, Suzuki T, Takehara S, Oshimura M, Kazuki Y.

Scientific  Reports. 2021 Oct 8;11(1):20050. doi: 10.1038/s41598-021-99535-y.

PITX1 inhibits the growth and proliferation of melanoma cells through regulation of SOX family genes.

Ohira T, Nakagawa S, Takeshita J, Aburatani H, Kugoh H.

Scientific Reports. 2021 Sep 15;11(1):18405. doi: 10.1038/s41598-021-97791-6.

Predicting quantitatively P-glycoprotein mediated drug-drug interactions and intestinal absorption using humanized mice

Miyake T, Tsutsui H, Haraya K, Tachibana T, Morimoto K, Takehara S, Ayabe M, Kobayashi K, Kazuki Y.

British Journal of Pharmacology. 2021 Jul 7. doi: 10.1111/bph.15612. 

Human chromosome 3p21.3 carries TERT transcriptional regulators in pancreatic cancer.

Takuki Yagyu, Takahito Ohira, Ryutaro Shimizu, Masaki Morimoto, Yuki Murakami, Takehiko Hanaki, Kyoichi Kihara, Tomoyuki Matsunaga, Manabu Yamamoto, Naruo Tokuyasu, Teruhisa Sakamoto, Yoshiyuki Fujiwara & Hiroyuki Kugoh 

Scientific Reports. volume 11 : 15355 (2021) 

Down syndrome-related transient abnormal myelopoiesis is attributed to a specific erythro-megakaryocytic subpopulation with GATA1 mutation.

Nishinaka-Arai Y, Niwa A, Matsuo S, Kazuki Y, Yakura Y, Hiroma T, Toki T, Sakuma T, Yamamoto T, Ito E, Oshimura M, Nakahata T, Saito MK.

Haematologica. 2021 Feb 1;106(2):635-640. doi: 10.3324/haematol.2019.242693.

Engineering of human induced pluripotent stem cells via human artificial chromosome vectors for cell therapy and disease modeling.

Kazuki Y, Uno N, Abe S, Kajitani N, Kazuki K, Yakura Y, Sawada C, Takata S, Sugawara M, Nagashima Y, Okada A, Hiratsuka M, Osaki M, Ferrari G, Tedesco FS, Nishikawa S, Fukumoto K, Takayanagi SI, Kunisato A, Kaneko S, Oshimura M, Tomizuka K.

Mol Ther Nucleic Acids. 2020 Dec 19;23:629-639. doi: 10.1016/j.omtn.2020.12.012. eCollection 2021 Mar 5.

Bioluminescence Measurement of Time-Dependent Dynamic Changes of CYP-Mediated Cytotoxicity in CYP-Expressing Luminescent HepG2 Cells.

Iwado S, Abe S, Oshimura M, Kazuki Y, Nakajima Y.

Int J Mol Sci. 2021 Mar 11;22(6):2843. doi: 10.3390/ijms22062843.

A novel all-in-one conditional knockout system uncovered an essential role of DDX1 in ribosomal RNA processing.

Suzuki T, Katada E, Mizuoka Y, Takagi S, Kazuki Y, Oshimura M, Shindo M, Hara T.

Nucleic Acids Res. 2021 Apr 19;49(7):e40. doi: 10.1093/nar/gkaa1296.

Pluripotent stem cell model of early hematopoiesis in Down syndrome reveals quantitative effects of short-form GATA1 protein on lineage specification.

Matsuo S, Nishinaka-Arai Y, Kazuki Y, Oshimura M, Nakahata T, Niwa A, Saito MK.

PLoS One. 2021 Mar 29;16(3):e0247595. doi: 10.1371/journal.pone.0247595. eCollection 2021.

Establishment of FXS-A9 panel with a single human X chromosome from fragile X syndrome-associated individual

Nakayama Y, Adachi K, Shioda N, Maeta S, Nanba E, Kugoh H.

Exp Cell Res. 2021 Jan 15;398(2):112419. doi: 10.1016/j.yexcr.2020.112419. 

CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor/ataxia syndrome

Asamitsu S, Yabuki Y, Ikenoshita S, Kawakubo K, Kawasaki M, Usuki S, Nakayama Y, Adachi K, Kugoh H, Ishii K, Matsuura T, Nanba E, Sugiyama H, Fukunaga K, Shioda N.

Science Advances 3 Jan 2021:Vol. 7, no. 3, eabd9440

DOI: 10.1126/sciadv.abd9440

A non-mosaic transchromosomic mouse model of Down syndrome carrying the long arm of human chromosome 21.

Yasuhiro Kazuki, Feng J. Gao, Yicong Li, Anna J. Moyer, Benjamin Devenney,
Kei Hiramatsu, Sachiko Miyagawa-Tomita, Satoshi Abe, Kanako Kazuki,
Naoyo Kajitani, Narumi Uno, Shoko Takehara, Masato Takiguchi, Miho
Yamakawa, Atsushi Hasegawa, Ritsuko Shimizu, Satoko Matsukura, Naohiro
Noda, Narumi Ogonuki, Kimiko Inoue, Shogo Matoba, Atsuo Ogura, Liliana
D. Florea, Alena Savonenko, Meifang Xiao, Dan Wu, Denise A.S. Batista,
Junhua Yang, Zhaozhu Qiu, Nandini Singh, Joan T. Richtsmeier, Takashi
Takeuchi, Mitsuo Oshimura and Roger H. Reeves

eLife. 2020. Jun 29;9:e56223. doi: 10.7554/eLife.56223.

A novel Xist RNA-mediated chromosome inactivation model using a mouse artificial chromosome.

Inaoka D, Sunamura N, Ohira T, Nakayama Y, Kugoh H.

Biotechnol Lett. 2020 Jan 31. doi: 10.1007/s10529-020-02826-z.

An efficient protein production system via gene amplification on a human artificial chromosome and the chromosome transfer to CHO cells.

Takahito Ohira, Koichi Miyauchi, Narumi Uno, Noriaki Shimizu, Yasuhiro Kazuki, Mitsuo Oshimura & Hiroyuki Kugoh.

Sci Rep 9, 16954 (2019) doi:10.1038/s41598-019-53116-2

PITX1 protein interacts with ZCCHC10 to regulate hTERT mRNA transcription.

Humanized UGT2 and CYP3A transchromosomic rats for improved prediction of human drug metabolism.

Comparison of the hepatic metabolism of triazolam in wild-type and Cyp3a-knockout mice for understanding CYP3A-mediated metabolism in CYP3A-humanised mice in vivo.

Generation of a novel isogenic trisomy panel in human embryonic stem cells via microcell-mediated chromosome transfer.

Possible Relationship Between MYBL1 Alterations and Specific Primary Sites in Adenoid Cystic Carcinoma: A Clinicopathological and Molecular Study of 36 Cases.

A luciferase complementation assay system using transferable mouse artificial chromosomes to monitor protein-protein interactions mediated by G protein-coupled receptors.

Evaluation of 4β-Hydroxycholesterol and 25-Hydroxycholesterol as Endogenous Biomarkers of CYP3A4: Study with CYP3A-Humanized Mice.

Characterization of P-Glycoprotein Humanized Mice Generated by Chromosome Engineering Technology: Its Utility for Prediction of Drug Distribution to the Brain in Humans.

Production of a Human Cell Line with a Plant Chromosome.

Development of a multiple-gene-loading method by combining multi-integration system-equipped mouse artificial chromosome vector and CRISPR-Cas9.

Bioluminescence-based cytotoxicity assay for simultaneous evaluation of cell viability and membrane damage in human hepatoma HepG2 cells.

Human and mouse artificial chromosome technologies for studies of pharmacokinetics and toxicokinetics.

Reversible immortalisation enables genetic correction of human muscle progenitors and engineering of next-generation human artificial chromosomes for Duchenne muscular dystrophy.

Modification of single-nucleotide polymorphism in a fully humanized CYP3A mouse by genome editing technology.

CRISPR/Cas9-induced transgene insertion and telomere-associated truncation of a single human chromosome for chromosome engineering in CHO and A9 cells.

Transfer of a Mouse Artificial Chromosome into Spermatogonial Stem Cells Generates Transchromosomic Mice.

Gender difference of hepatic and intestinal CYP3A4 in CYP3A-humanized mice generated by a human chromosome-engineering technique.

Kobayashi K, Abe C, Endo M, Kazuki Y, Oshimura M, Chiba K.

Drug Metab Lett. 2017 Apr 4. doi: 10.2174/1872312811666170404153804.

Multiple expression cassette exchange via TP901-1, R4, and Bxb1 integrase systems on a mouse artificial chromosome.

Tomimatsu K, Kokura K, Nishida T, Yoshimura Y, Kazuki Y, Narita M, Oshimura M, Ohbayashi T.

FEBS Open Bio. 2017 Jan 28;7(3):306-317. doi: 10.1002/2211-5463.12169. eCollection 2017 Mar.

Development of Caco-2 cells co-expressing CYP3A4 and NADPH-cytochrome P450 reductase using a human artificial chromosome for the prediction of intestinal extraction ratio of CYP3A4 substrates.

Takenaka T, Kazuki K, Harada N, Kuze J, Chiba M, Iwao T, Matsunaga T, Abe S, Oshimura M, Kazuki Y.

Drug Metab Pharmacokinet. 2017 Feb;32(1):61-68. doi: 10.1016/j.dmpk.2016.08.004. Epub 2016 Aug 26.

Correlation between luminescence intensity and cytotoxicity in cell-based cytotoxicity assay using luciferase.

Wakuri S, Yamakage K, Kazuki Y, Kazuki K, Oshimura M, Aburatani S, Yasunaga M, Nakajima Y.

Anal Biochem. 2017 Apr 1;522:18-29. doi: 10.1016/j.ab.2017.01.015. Epub 2017 Jan 20.

Maintenance and Function of a Plant Chromosome in Human Cells.

Wada N, Kazuki Y, Kazuki K, Inoue T, Fukui K, Oshimura M.

ACS Synth Biol. 2017 Feb 17;6(2):301-310. doi: 10.1021/acssynbio.6b00180. Epub 2016 Oct 17.

A kidney injury molecule-1 (Kim-1) gene reporter in a mouse artificial chromosome: the responsiveness to cisplatin toxicity in immortalized mouse kidney S3 cells.

Kokura K, Kuromi Y, Endo T, Anzai N, Kazuki Y, Oshimura M, Ohbayashi T.

J Gene Med. 2016 Oct;18(10):273-281. doi: 10.1002/jgm.2925.

Allogeneic transplantation of iPS cell-derived cardiomyocytes regenerates primate hearts.

Shiba Y, Gomibuchi T, Seto T, Wada Y, Ichimura H, Tanaka Y, Ogasawara T, Okada K, Shiba N, Sakamoto K, Ido D, Shiina T, Ohkura M, Nakai J, Uno N, Kazuki Y, Oshimura M, Minami I, Ikeda U.

Nature. 2016 Oct 20;538(7625):388-391. doi: 10.1038/nature19815. Epub 2016 Oct 10.

Effects of duration of electric pulse on in vitro development of cloned cat embryos with human artificial chromosome vector.

Do L, Wittayarat M, Terazono T, Sato Y, Taniguchi M, Tanihara F, Takemoto T, Kazuki Y, Kazuki K, Oshimura M, Otoi T.

Reprod Domest Anim. 2016 Dec;51(6):1039-1043. doi: 10.1111/rda.12766. Epub 2016 Aug 28.

Evaluation of an Hprt-Luciferase Reporter Gene on a Mammalian Artificial Chromosome in Response to Cytotoxicity.

Endo T, Noda N, Kuromi Y, Kokura K, Kazuki Y, Oshimura M, Ohbayashi T.

Yonago Acta Med. 2016 Jun 29;59(2):174-82. eCollection 2016 Jun.

Induction of genomic instability and activation of autophagy in artificial human aneuploid cells.

Ariyoshi K, Miura T, Kasai K, Fujishima Y, Oshimura M, Yoshida MA.

Mutat Res. 2016 Aug;790:19-30. doi: 10.1016/j.mrfmmm.2016.06.001. Epub 2016 Jun 14.

Highly Efficient Transfer of Chromosomes to a Broad Range of Target Cells Using Chinese Hamster Ovary Cells Expressing Murine Leukemia Virus-Derived Envelope Proteins.

Suzuki T, Kazuki Y, Oshimura M, Hara T.

PLoS One. 2016 Jun 7;11(6):e0157187. doi: 10.1371/journal.pone.0157187. eCollection 2016.

Concordant but Varied Phenotypes among Duchenne Muscular Dystrophy Patient-Specific Myoblasts Derived using a Human iPSC-Based Model.

Choi IY, Lim H, Estrellas K, Mula J, Cohen TV, Zhang Y, Donnelly CJ, Richard JP, Kim YJ, Kim H, Kazuki Y, Oshimura M, Li HL, Hotta A, Rothstein J, Maragakis N, Wagner KR, Lee G.

Cell Rep. 2016 Jun 7;15(10):2301-12. doi: 10.1016/j.celrep.2016.05.016. Epub 2016 May 26.

A Cytoplasmic Form of Gaussia luciferase Provides a Highly Sensitive Test for Cytotoxicity.

Tsuji S, Ohbayashi T, Yamakage K, Oshimura M, Tada M.

PLoS One. 2016 May 26;11(5):e0156202. doi: 10.1371/journal.pone.0156202. eCollection 2016.

Cyp3a deficiency enhances androgen receptor activity and cholesterol synthesis in the mouse prostate.

Hashimoto M, Kobayashi K, Yamazaki M, Kazuki Y, Takehara S, Oshimura M, Chiba K.

J Steroid Biochem Mol Biol. 2016 Oct;163:121-8. doi: 10.1016/j.jsbmb.2016.04.018. Epub 2016 Apr 29.

Dynamics of epigenetic regulation at the single-cell level.

Bintu L, Yong J, Antebi YE, McCue K, Kazuki Y, Uno N, Oshimura M, Elowitz MB.

Science. 2016 Feb 12;351(6274):720-4. doi: 10.1126/science.aab2956.

Thalidomide-induced limb abnormalities in a humanized CYP3A mouse model.

Kazuki Y, Akita M, Kobayashi K, Osaki M, Satoh D, Ohta R, Abe S, Takehara S, Kazuki K, Yamazaki H, Kamataki T, Oshimura M.

Sci Rep. 2016 Feb 23;6:21419. doi: 10.1038/srep21419.

Regulation of functional KCNQ1OT1 lncRNA by β-catenin.

Studies of Tumor Suppressor Genes via Chromosome Engineering.

Development of a Safeguard System Using an Episomal Mammalian Artificial Chromosome for Gene and Cell Therapy.

Repression of hTERT transcription by the introduction of chromosome 3 into human oral squamous cell carcinoma.

Construction of a Luciferase Reporter System to Monitor Osteogenic Differentiation of Mesenchymal Stem Cells by Using a Mammalian Artificial Chromosome Vector.

Retargeting of microcell fusion towards recipient cell-oriented transfer of human artificial chromosome.

Recurrent micronucleation through cell cycle progression in the presence of microtubule inhibitors.

A pathway from chromosome transfer to engineering resulting in human and mouse artificial chromosomes for a variety of applications to bio-medical challenges.

miR-19b regulates hTERT mRNA expression through targeting PITX1 mRNA in melanoma cells.