Yusa Group | Stem Cell Genetics

Yusa Group | Stem Cell Genetics

Yusa Group

Yusa GroupSanger Institute, Genome Research Limited
Yusa Group

Our Research and Approach

The Yusa laboratory focuses on the development of genome engineering technologies that allow us to perform unbiased genome-wide genetic screens in mammalian cells. We have recently adopted the CRISPR-Cas9 technology as a screening tool and generated genome-scale lentiviral CRISPR libraries. The current focus of the laboratory is further development and improvement of the CRISPR screening methodology and application of the screening technology in stem cell and oncology research.

Stem cell biology: Maintenance of and exit from pluripotency in mouse and human ES/iPS cells. Differentiation. Lineage reprogramming.

Oncology: Genetic vulnerabilities in cancer cells. The mechanisms of drug resistance. Sensitisation to targeted therapies.

People

Yusa, Kosuke
Dr Kosuke Yusa
Group Leader

Group Leader of Team 203 Stem Cell Genetics


Research Programmes

Partners and Funders

Internal Partners

Publications

  • Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.

    Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera Mdel C and Yusa K

    Nature biotechnology 2014;32;3;267-73

  • Seamless genome editing in human pluripotent stem cells using custom endonuclease-based gene targeting and the piggyBac transposon.

    Yusa K

    Nature protocols 2013;8;10;2061-78

  • Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells.

    Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu PQ et al.

    Nature 2011;478;7369;391-4

  • Optimised metrics for CRISPR-KO screens with second-generation gRNA libraries.

    Ong SH, Li Y, Koike-Yusa H and Yusa K

    Scientific reports 2017;7;1;7384

  • Applications of CRISPR Genome Editing Technology in Drug Target Identification and Validation.

    Lu Q, Livi GP, Modha S, Yusa K, Macarrón R and Dow DJ

    Expert opinion on drug discovery 2017

  • A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia.

    Tzelepis K, Koike-Yusa H, De Braekeleer E, Li Y, Metzakopian E et al.

    Cell reports 2016;17;4;1193-1205

  • Mutational History of a Human Cell Lineage from Somatic to Induced Pluripotent Stem Cells.

    Rouhani FJ, Nik-Zainal S, Wuster A, Li Y, Conte N et al.

    PLoS genetics 2016;12;4;e1005932

  • piggyBac Transposon.

    Yusa K

    Microbiology spectrum 2015;3;2;MDNA3-0028-2014

  • Off-target assessment of CRISPR-Cas9 guiding RNAs in human iPS and mouse ES cells.

    Tan EP, Li Y, Velasco-Herrera Mdel C, Yusa K and Bradley A

    Genesis (New York, N.Y. : 2000) 2015;53;2;225-36

  • Removal of reprogramming transgenes improves the tissue reconstitution potential of keratinocytes generated from human induced pluripotent stem cells.

    Igawa K, Kokubu C, Yusa K, Horie K, Yoshimura Y et al.

    Stem cells translational medicine 2014;3;9;992-1001

  • Genome-wide recessive genetic screening in mammalian cells with a lentiviral CRISPR-guide RNA library.

    Koike-Yusa H, Li Y, Tan EP, Velasco-Herrera Mdel C and Yusa K

    Nature biotechnology 2014;32;3;267-73

  • Seamless genome editing in human pluripotent stem cells using custom endonuclease-based gene targeting and the piggyBac transposon.

    Yusa K

    Nature protocols 2013;8;10;2061-78

  • Enhancement of microhomology-mediated genomic rearrangements by transient loss of mouse Bloom syndrome helicase.

    Yamanishi A, Yusa K, Horie K, Tokunaga M, Kusano K et al.

    Genome research 2013;23;9;1462-73

  • Nuclear Wave1 is required for reprogramming transcription in oocytes and for normal development.

    Miyamoto K, Teperek M, Yusa K, Allen GE, Bradshaw CR and Gurdon JB

    Science (New York, N.Y.) 2013;341;6149;1002-5

  • A genetic progression model of Braf(V600E)-induced intestinal tumorigenesis reveals targets for therapeutic intervention.

    Rad R, Cadiñanos J, Rad L, Varela I, Strong A et al.

    Cancer cell 2013;24;1;15-29

  • The piggyBac transposon displays local and distant reintegration preferences and can cause mutations at noncanonical integration sites.

    Li MA, Pettitt SJ, Eckert S, Ning Z, Rice S et al.

    Molecular and cellular biology 2013;33;7;1317-30

  • Hyperactive piggyBac gene transfer in human cells and in vivo.

    Doherty JE, Huye LE, Yusa K, Zhou L, Craig NL and Wilson MH

    Human gene therapy 2012;23;3;311-20

  • The critical role of histone H2A-deubiquitinase Mysm1 in hematopoiesis and lymphocyte differentiation.

    Nijnik A, Clare S, Hale C, Raisen C, McIntyre RE et al.

    Blood 2012;119;6;1370-9

  • Mobilization of giant piggyBac transposons in the mouse genome.

    Li MA, Turner DJ, Ning Z, Yusa K, Liang Q et al.

    Nucleic acids research 2011;39;22;e148

  • A homozygous mutant embryonic stem cell bank applicable for phenotype-driven genetic screening.

    Horie K, Kokubu C, Yoshida J, Akagi K, Isotani A et al.

    Nature methods 2011;8;12;1071-7

  • Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells.

    Yusa K, Rashid ST, Strick-Marchand H, Varela I, Liu PQ et al.

    Nature 2011;478;7369;391-4

  • Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells.

    LaRocque JR, Stark JM, Oh J, Bojilova E, Yusa K et al.

    Proceedings of the National Academy of Sciences of the United States of America 2011;108;29;11971-6

  • A hyperactive piggyBac transposase for mammalian applications.

    Yusa K, Zhou L, Li MA, Bradley A and Craig NL

    Proceedings of the National Academy of Sciences of the United States of America 2011;108;4;1531-6

  • PiggyBac transposon mutagenesis: a tool for cancer gene discovery in mice.

    Rad R, Rad L, Wang W, Cadinanos J, Vassiliou G et al.

    Science (New York, N.Y.) 2010;330;6007;1104-7

  • Butyrate greatly enhances derivation of human induced pluripotent stem cells by promoting epigenetic remodeling and the expression of pluripotency-associated genes.

    Mali P, Chou BK, Yen J, Ye Z, Zou J et al.

    Stem cells (Dayton, Ohio) 2010;28;4;713-20

  • Fezf1 is required for penetration of the basal lamina by olfactory axons to promote olfactory development.

    Watanabe Y, Inoue K, Okuyama-Yamamoto A, Nakai N, Nakatani J et al.

    The Journal of comparative neurology 2009;515;5;565-84

  • Generation of transgene-free induced pluripotent mouse stem cells by the piggyBac transposon.

    Yusa K, Rad R, Takeda J and Bradley A

    Nature methods 2009;6;5;363-9

  • Sleeping beauty transposase has an affinity for heterochromatin conformation.

    Ikeda R, Kokubu C, Yusa K, Keng VW, Horie K and Takeda J

    Molecular and cellular biology 2007;27;5;1665-76

  • Rad54 is dispensable for the ALT pathway.

    Akiyama K, Yusa K, Hashimoto H, Poonepalli A, Hande MP et al.

    Genes to cells : devoted to molecular & cellular mechanisms 2006;11;11;1305-15

  • Sleeping beauty transposon-based phenotypic analysis of mice: lack of Arpc3 results in defective trophoblast outgrowth.

    Yae K, Keng VW, Koike M, Yusa K, Kouno M et al.

    Molecular and cellular biology 2006;26;16;6185-96

  • Bloom's syndrome gene-deficient phenotype in mouse primary cells induced by a modified tetracycline-controlled trans-silencer.

    Hayakawa T, Yusa K, Kouno M, Takeda J and Horie K

    Gene 2006;369;80-9

  • Region-specific saturation germline mutagenesis in mice using the Sleeping Beauty transposon system.

    Keng VW, Yae K, Hayakawa T, Mizuno S, Uno Y et al.

    Nature methods 2005;2;10;763-9

  • Genome-wide phenotype analysis in ES cells by regulated disruption of Bloom's syndrome gene.

    Yusa K, Horie K, Kondoh G, Kouno M, Maeda Y et al.

    Nature 2004;429;6994;896-9

  • Enhancement of Sleeping Beauty transposition by CpG methylation: possible role of heterochromatin formation.

    Yusa K, Takeda J and Horie K

    Molecular and cellular biology 2004;24;9;4004-18

  • Characterization of Sleeping Beauty transposition and its application to genetic screening in mice.

    Horie K, Yusa K, Yae K, Odajima J, Fischer SE et al.

    Molecular and cellular biology 2003;23;24;9189-207