Woltjen Lab

Stem Cells and Genome Engineering


Research Articles
Review Articles
Invited Publications, Book Chapters

PubMed // Google Scholar // Research Map // ORCID

Research Articles


Capturing Human Trophoblast Development with Naive Pluripotent Stem Cells in Vitro. Io, S., Kabata, M., Iemura, Y., Semi, K., Morone, N., Minagawa, A., Wang, B., Okamoto, I., Nakamura, T., Kojima, Y., Iwatani, C., Tsuchiya, H., Kaswandy, B., Kondoh, E., Kaneko, S., Woltjen, K., Saitou, M., Yamamoto, T., Mandai, M. and Takashima, Y. (2021) Cell Stem Cell.

Epithelial Expression of Gata4 and Sox2 Regulates Specification of the Squamous-Columnar Junction via MAPK/ERK Signaling in Mice. Sankoda, N., Tanabe, W., Tanaka, A., Shibata, H., Woltjen, K., Chiba, T., Haga, H., Sakai, Y., Mandai, M., Yamamoto, T., Yamada, Y., Uemoto, S. and Kawaguchi, Y. (2021) Nature communications, 12, 560.


Synergistic gene editing in human iPS cells via cell cycle and DNA repair modulation. Maurissen, T.L. and Woltjen, K. (2020) Nature communications, 11, 2876.

Recapitulating the Human Segmentation Clock with Pluripotent Stem Cells. Matsuda, M., Yamanaka, Y., Uemura, M., Osawa, M., Saito, M.K., Nagahashi, A., Nishio, M., Guo, L., Ikegawa, S., Sakurai, S., Kihara, S., Maurissen, T.L., Nakamura, M., Matsumoto, T., Yoshitomi, H., Ikeya, M., Kawakami, N., Yamamoto, T., Woltjen, K., Ebisuya, M., Toguchida, J. and Alev, C. (2020) Nature, 580, 124–129.

N-Terminal Amino Acids Determine KLF4 Protein Stability in 2A Peptide-Linked Polycistronic Reprogramming Constructs. Reinhardt, A., Kagawa, H. and Woltjen, K. (2020) Stem Cell Reports, 14, 520–527.


Genome-Wide Microhomologies Enable Precise Template-Free Editing of Biologically Relevant Deletion Mutations. Grajcarek, J., Monlong, J., Nishinaka-Arai, Y., Nakamura, M., Nagai, M., Matsuo, S., Lougheed, D., Sakurai, H., Saito, M.K., Bourque, G. and Woltjen, K. (2019) Nature communications, 10, 4856.

Metalloprotease-Dependent Attenuation of BMP Signaling Restricts Cardiac Neural Crest Cell Fate. Arai, H.N., Sato, F., Yamamoto, T., Woltjen, K., Kiyonari, H., Yoshimoto, Y., Shukunami, C., Akiyama, H., Kist, R. and Sehara-Fujisawa, A. (2019) Cell Reports, 29, 603–616.

Cell-Type Dependent Enhancer Binding of the EWS/ATF1 Fusion Gene in Clear Cell Sarcomas. Komura, S., Ito, K., Ohta, S., Ukai, T., Kabata, M., Itakura, F., Semi, K., Matsuda, Y., Hashimoto, K., Shibata, H., Sone, M., Jo, N., Sekiguchi, K., Ohno, T., Akiyama, H., Shimizu, K., Woltjen, K., Ozawa, M., Toguchida, J., Yamamoto, T. and Yamada, Y. (2019) Nature communications, 10, 3999.


OVOL1 Influences the Determination and Expansion of iPSC Reprogramming Intermediates. Kagawa, H., Shimamoto, R., Kim, S.-I., Oceguera-Yanez, F., Yamamoto, T., Schroeder, T. and Woltjen, K. (2018) Stem Cell Reports, 12, 319–332.

Platforms of in Vivo Genome Editing with Inducible Cas9 for Advanced Cancer Modeling. Jo, N., Sogabe, Y., Yamada, Y., Ukai, T., Kagawa, H., Mitsunaga, K., Woltjen, K. and Yamada, Y. (2018) Cancer science, 110, 926–938.

Microhomology-Assisted Scarless Genome Editing in Human iPSCs. Kim, S.-I., Matsumoto, T., Kagawa, H., Nakamura, M., Hirohata, R., Ueno, A., Ohishi, M., Sakuma, T., Soga, T., Yamamoto, T. and Woltjen, K. (2018) Nature communications, 9, 939.
Press releases: CiRA Website (日本語 or English), and EurekAlert!
[PubMed][Journal Home][Enhanced PDF]

In Vivo Reprogramming Drives Kras-Induced Cancer Development. Shibata, H., Komura, S., Yamada, Y., Sankoda, N., Tanaka, A., Ukai, T., Kabata, M., Sakurai, S., Kuze, B., Woltjen, K., Haga, H., Ito, Y., Kawaguchi, Y., Yamamoto, T. and Yamada, Y. (2018) Nature communications, 9, 1–16

Srf Destabilizes Cellular Identity by Suppressing Cell- Type-Specific Gene Expression Programs. Ikeda, T., Hikichi, T., Miura, H., Shibata, H., Mitsunaga, K., Yamada, Y., Woltjen, K., Miyamoto, K., Hiratani, I., Yamada, Y., Hotta, A., Yamamoto, T., Okita, K. and Masui, S. (2018) Nature communications, 1–15.


Evolutionarily Distinctive Transcriptional and Signaling Programs Drive Human Germ Cell Lineage Specification From Pluripotent Stem Cells. Kojima, Y., Sasaki, K., Yokobayashi, S., Sakai, Y., Nakamura, T., Yabuta, Y., Nakaki, F., Nagaoka, S., Woltjen, K., Hotta, A., Yamamoto, T. and Saitou, M. (2017) Cell Stem Cell, 21, 517–532.e5.

Cell-Type-Specific Genome Editing with a microRNA-Responsive CRISPR-Cas9 Switch. Hirosawa, M., Fujita, Y., Parr, C.J.C., Hayashi, K., Kashida, S., Hotta, A., Woltjen, K. and Saito, H. (2017) Nucleic Acids Research, 45, e118.

The Src/C-Abl Pathway Is a Potential Therapeutic Target in Amyotrophic Lateral Sclerosis. Imamura, K., Izumi, Y., Watanabe, A., Tsukita, K., Woltjen, K., Yamamoto, T., Hotta, A., Kondo, T., Kitaoka, S., Ohta, A., Tanaka, A., Watanabe, D., Morita, M., Takuma, H., Tamaoka, A., Kunath, T., Wray, S., Furuya, H., Era, T., Makioka, K., Okamoto, K., Fujisawa, T., Nishitoh, H., Homma, K., Ichijo, H., Julien, J.-P., Obata, N., Hosokawa, M., Akiyama, H., Kaneko, S., Ayaki, T., Ito, H., Kaji, R., Takahashi, R., Yamanaka, S. and Inoue, H. (2017) Science Translational Medicine, 9 (391).

Hybrid Cellular Metabolism Coordinated by Zic3 and Esrrb Synergistically Enhances Induction of Naive Pluripotency. Sone, M., Morone, N., Nakamura, T., Tanaka, A., Okita, K., Woltjen, K., Nakagawa, M., Heuser, J.E., Yamada, Y., Yamanaka, S. and Yamamoto, T. (2017) Cell Metabolism, 25, 1103–1117.e6.

Cellular Context-Dependent Consequences of Apc Mutations on Gene Regulation and Cellular Behavior. Hashimoto, K., Yamada, Y., Semi, K., Yagi, M., Tanaka, A., Itakura, F., Aoki, H., Kunisada, T., Woltjen, K., Haga, H., Sakai, Y., Yamamoto, T. and Yamada, Y. (2017) Proceedings of the National Academy of Sciences, 114, 758–763.


An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development. Komura, S., Semi, K., Itakura, F., Shibata, H., Ohno, T., Hotta, A., Woltjen, K., Yamamoto, T., Akiyama, H. and Yamada, Y. (2016) Stem Cell Reports, 6, 592–606.

Engineering the AAVS1 locus for consistent and scalable transgene expression in human iPSCs and their differentiated derivatives. Oceguera-Yanez, F., Kim, S-I., Matsumoto, T., Tan, G. W., Xiang, L., Hatani, T., Kondo, T., Ikeya, M., Yoshida, Y., Inoue, H. and Woltjen, K. (2016). Methods. (San Diego, Calif).


KLF4 N-Terminal Variance Modulates Induced Reprogramming to Pluripotency. Kim S-I, Oceguera-Yanez F., Hirohata R., Linker S., Okita K., Yamada Y., Yamamoto T., Yamanaka S. and Woltjen K. (2015). Stem Cell Reports. 4, 1-17.
Highlighted by Faculty of 1000
See the press release on the CiRA Website (日本語 or English), and on EurekAlert!
[PubMed][Journal Home]

Reprogramming Roadblocks Are System Dependent. Chantzoura, E., Skylaki, S., Menendez, S., Kim, S.-I., Johnsson, A., Linnarsson, S., Woltjen, K., Chambers, I. and Kaji, K. (2015). Stem Cell Reports. 5(3), 350–364.

Robust In Vitro Induction of Human Germ Cell Fate from Pluripotent Stem Cells. Sasaki, K., Yokobayashi, S., Nakamura, T., Okamoto, I., Yabuta, Y., Kurimoto, K., Ohta, H., Moritoki, Y., Iwatani, C., Tsuchiya, H., Nakamura, S., Sekiguchi, K., Sakuma, T., Yamamoto, T., Mori, T., Woltjen, K., Nakagawa, M., Yamamoto, T., Takahashi, K., Yamanaka, S. and Saitou, M. (2015). Cell Stem Cell. 17(2), 178–194.

Mutant IDH1 Dysregulates the Differentiation of Mesenchymal Stem Cells in Association with Gene-Specific Histone Modifications to Cartilage- and Bone-Related Genes. Jin, Y., Elalaf, H., Watanabe, M., Tamaki, S., Hineno, S., Matsunaga, K., Woltjen, K., Kobayashi, Y., Nagata, S., Ikeya, M., Kato, T., Okamoto, T., Matsuda, S. and Toguchida J. (2015). PLoS ONE. 10(7), e0131998.

SS18-SSX, the Oncogenic Fusion Protein in Synovial Sarcoma, Is a Cellular Context-Dependent Epigenetic Modifier. Tamaki, S., Fukuta, M., Sekiguchi, K., Jin, Y., Nagata, S., Hayakawa, K., Hineno, S., Okamoto, T., Watanabe, M., Woltjen, K., Ikeya, M., Kato, T. and Toguchida, J. (2015). PLoS ONE. 10(11), e0142991.

Synthetic lateral inhibition governs cell-type bifurcation with robust ratios. Matsuda M., Koga M., Woltjen K., Nishida E., and Ebisuya M. (2015). Nature Communications. 6, 6195.
[PubMed][Journal Home]


Premature termination of reprogramming in vivo leads to cancer development through altered epigenetic regulation. Ohnishi K., Semi K., Yamamoto T., Shimizu M., Tanaka A., Mitsunaga K., Okita K., Osafune K., Arioka Y., Maeda T., Soejima H., Moriwaki H., Yamanaka S., Woltjen K., and Yamada Y. (2014). Cell. 156(4), 663-677.
Discussed in a Cell Stem Cell Preview by Jose Polo
[PubMed][Journal Home]


Transient maternal IL-6 mediates long-lasting changes in neural stem cell pools by deregulating an endogenous self-renewal pathway. Gallagher D., Norman A. A., Woodard C. L., Yang G., Gauthier-Fisher A., Fujitani M., Vessey J.P., Cancino G.I., Sachewsky N., Woltjen K., Fatt M.P., Morshead C.M., Kaplan D.R. and Miller F.D. (2013). Cell Stem Cell. 13(5), 564-576.
Discussed in a Cell Stem Cell Preview by Elizabeth Gould
[PubMed][Journal Home]

Cartilage tissue engineering identifies abnormal human induced pluripotent stem cells. Yamashita A., Liu S., Woltjen K., Thomas B., Meng G., Hotta A., Takahashi K., Ellis J., Yamanaka S. and Rancourt D.E. (2013). Scientific Reports. 3(1978).
[PubMed][Journal Home]

Efficient and reproducible myogenic differentiation from human iPS cells: prospects for modeling Miyoshi Myopathy in vitro. Tanaka A., Woltjen K., Miyake K., Hotta A., Ikeya M., Yamamoto T., Nishino T., Shoji E., Sehara-Fujisawa A., Manabe Y., Fujii N., Hanaoka K., Era T., Yamashita S., Isobe K., Kimura E. and Sakurai H.. (2013). PLoS One. 8(4), e61540.
[PubMed][Journal Home]

Efficient TALEN construction and evaluation methods for human cell and animal applications. Sakuma T., Hosoi S., Woltjen K., Suzuki K.I., Kashiwagi K, Wada H., Ochiai H., Miyamoto T., Kawai N., Sasakura Y., Matsuura S., Okada Y., Kawahara A., Hayashi S. and Yamamoto T. (2013). Genes to Cells. 18(4), 315-326.
[PubMed][Journal Home]

Identification of target genes of synovial sarcoma-associated fusion oncoprotein using human pluripotent stem cells. Hayakawa, K., Ikeya, M., Fukuta, M., Woltjen K., Tamaki, S., Takahara, N., Kato, T., Sato, S., Otsuka, T. and Toguchida, J. (2013). Biochem. Biophys. Research Communications. 432(4), 713-719.
[PubMed][Journal Home]


Highly efficient site-specific transgenesis in cancer cell lines. Michael, I.P., Monetti, C., Chiu, A.C., Zhang, P., Baba, T., Nishino, K., Agha-Mohammadi, S., Woltjen K., Sung, H.K. and Nagy, A. (2012). Molecular Cancer. 11(1), 89-100.
[PubMed] [Journal Home]


An alternative splicing switch regulates embryonic stem cell pluripotency and reprogramming. Gabut, M., Samavarchi-Tehrani, P., Wang, X., Slobodeniuc, V., O’Hanlon, D., Sung, H-K., Alvarez, M., Talukder, S., Pan, Q., Mazzoni, E.O., Nedelec, S., Wichterle, H., Woltjen K., Hughes, T.R., Zandstra, P.W., Nagy, A., Wrana, J.L., Blencowe, B.J. (2011). Cell. 147(1), 132-146.
Article Selected for a 2012 Lap-Chee Tsui Publication Award from the CIHR Institute of Genetics
[PubMed] [Journal Home]

Induced Pluripotent Stem Cell Lines Derived from Equine Fibroblasts. Nagy, K., Sung, H-K., Zhang, P., Laflamme, S., Vincent, P., Agha-Mohammadi, S., Woltjen K., Monetti, C., Michael, I.P., Hussein, S., Smith, L.C., and Nagy, A. (2011). Stem Cell Reviews and Reports7(3), 693-702.
[Pubmed] [Journal Home]

PhiC31 integrase facilitates genetic approaches combining multiple recombinases. Monetti, C., Nishino, K., Biechele, S., Zhang, P., Baba, T., Woltjen K. and Nagy, A. (2011). Methods. 53(4), 380-385.
[PubMed] [Journal Home]


Functional Genomics Reveals a BMP Driven Mesenchymal-to-Epithelial Transition in the Initiation of Somatic Cell Reprogramming. Samavarchi-Tehrani, P., Golipour, A., David, L., Sung, H-K., Beyer, T.A., Datti, A., Woltjen K., Nagy, A., and Wrana, J.L. (2010). Cell Stem Cell. 7, 64-77.
Discussed in a Nature Methods News and Views by Konrad Hochedlinger
[PubMed] [Journal Home]

2009 and prior

Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Kaji, K., Norrby, K., Paca, A., Mileikovsky, M., Mohseni, P., and Woltjen K. (2009). Nature. 458, 771-775.
[PubMed] [Journal Home]

piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells.Woltjen K., Michael, I.P., Mohseni, P., Desai, R., Mileikovsky, M., Hämäläinen, R., Cowling, R., Wang, W., Liu, P., Gertsenstein, M., Kaji, K., Sung, HK., and Nagy A. (2009). Nature. 458, 766-770.
Highlighted in Nature Methods’ News and Views
[PubMed] [Journal Home]

Deep screening of recombination proficient bacteriophage libraries. Thomas, B., Woltjen K., and Rancourt, D.E. (2003). Biotechniques. 34, 36-38, 40.
[PubMed] [Journal Home]

Bacteriophage gene targeting vectors generated by transplacement. Aoyama, C., Woltjen K., Mansergh, F.C., Ishidate, K., and Rancourt, D.E. (2002). Biotechniques. 33, 806-810, 812.
[PubMed] [Journal Home]

Retro-recombination screening of a mouse embryonic stem cell genomic library. Woltjen K., Bain, G., and Rancourt, D.E. (2000). Nucleic Acids Research. 28, E41.
[PubMed] [Journal Home]

Top ∆

Review Articles

Editorial Overview: Embroidering the Canvas of Life. Woltjen, K. and Bortvin, A. (2018) Current opinion in genetics & development, 52, ii–iv.

Beta Cell Replacement Strategies for Diabetes. Kieffer, T.J., Woltjen, K., Osafune, K., Yabe, D. and Inagaki, N. (2017) Journal of Diabetes Investigation.

At the Conflux of Human Genome Engineering and Induced Pluripotency. Woltjen, K., Oceguera-Yanez, F., Kagawa, H. and Kim, S.-I. (2016) Genome Editing, Springer International Publishing, Cham, 45–64.

Nuclease-mediated genome editing: At the front-line of functional genomics technology. Sakuma T. and Woltjen K. (2014). Development, Growth and Differentiation. 56, 2-13.
[PubMed][Journal Home]

Reprogramming: The Next Generation. Hochedlinger, K., Takahashi, K., Plath, K., Ng, H.H., Clark, A., Martin, U., Hanna, J.H., Deng, H., Silva, J.C.R., Woltjen K., Boyer, L. and Wernig, M. (2012). Cell Stem Cell. 11(6), 740–743.
SPECIAL ISSUE! Highlighting the 2013 Nobel Prize in Medicine.
[Science Direct] [DOI] [Journal Home]

Inhibition of tgf-Beta signaling improves mouse fibroblast reprogramming. Woltjen K., and Stanford, W.L. (2009). Cell Stem Cell. 5, 457-458.
[PubMed] [Journal Home]

New strategies to generate induced pluripotent stem cells. O’Malley, J., Woltjen K., and Kaji, K. (2009). Current Opinion in Biotechnology. 20, 516-521.
[PubMed] [Journal Home]

Top ∆

Invited Publications, Book Chapters

健常人および患者に共通して観察される欠失変異に隣接した相同配列と正確なゲノム編集における相同配列の活用. Grajcarek, J., Lee, S., and Woltjen, K. (2020) 医学のあゆみ, 273:9, 744-750. (Chapter)

ヒトiPS細胞のAAVS1遺伝子座への遺伝子組込み. Lee, S., 香川, 晴., 松本, 智., Oceguera-Yanez, F. and Woltjen, K. (2019) In: 山本, 卓. and 佐久間, 哲., Eds., ゲノム編集実験スタンダード, 実験医学別冊, 205–220.

iPS細胞を用いた正確な ゲノム編集法(MhAX法). 香川, 晴., 松本, 智., Kim, S.-I. and Woltjen, K. (2018) 実験医学, 1–8.

Report on the Conference on Transposition and Genome Engineering 2015 (TGE 2015): Advancing Cutting-Edge Genomics Technology in the Ancient City of Nara. Woltjen, K., Yamamoto, T., Kokubu, C. and Takeda, J. (2016). Genes to cells. 392–395.

Inducible Transgene Expression in Human iPS Cells Using Versatile All-in-One piggyBac Transposons. Kim, S.-I., Oceguera-Yanez, F., Sakurai, C., Nakagawa, M., Yamanaka, S., & Woltjen, K. (2015). Methods in Molecular Biology (Clifton, NJ).

The piggyBac Transposon as a Platform Technology for Somatic Cell Reprogramming Studies in Mouse. Woltjen, K., Kim, S.-I., & Nagy, A. (2015). Methods in Molecular Biology (Clifton, NJ).

Directed Myogenic Differentiation of Human Induced Pluripotent Stem Cells. Shoji, E., Woltjen, K., & Sakurai, H. (2015). Methods in Molecular Biology (Clifton, NJ).

Transgene-free production of pluripotent stem cells using piggyBac transposons. Woltjen K., Hämäläinen, R., Kibschull, M., Mileikovsky, M., and Nagy, A. (2011). Methods in Molecular Biology767, 87-103.
[PubMed] [Journal Home]

Multiplex Gene-Expression Assay for Human Induced Pluripotent Stem Cells. Sciabica, K., Woltjen K., Hotta, A. (2010). Genetic Engineering and Biotechnology News. 30(3).
[Journal Home]

Orpheus recombination: a comprehensive bacteriophage system for murine targeting vector construction by transplacement. Woltjen K., Ito, K., Tsuzuki, T., and Rancourt, D.E. (2008). Methods in Molecular Biology. 435, 79-94.
[PubMed] [Journal Home]

Transplacement mutagenesis. A recombination-based in situ mutagenesis protocol. Woltjen K., Unger, M.W.T., and Rancourt, D.E. (2002). Methods in Molecular Biology. 182, 189-207.
[PubMed] [Journal Home]

Top ∆