Screening ethnically diverse human embryonic stem cells identifies a chromosome 20 minimal amplicon conferring growth advantage

Katherine Amps*, Peter W. Andrews, George Anyfantis, Lyle Armstrong, Stuart Avery, Hossein Baharvand, Julie Baker, Duncan Baker, Maria B. Munoz, Stephen Beil, Nissim Benvenisty, Dalit Ben-Yosef, Juan Carlos Biancotti, Alexis Bosman, Romulo Martin Brena, Daniel Brison, Gunilla Caisander, Marãa V. Camarasa, Jieming Chen, Eric ChiaoYoung Min Choi, Andre B.H. Choo, Daniel Collins, Alan Colman, Jeremy M. Crook, George Q. Daley, Anne Dalton, Paul A. De Sousa, Chris Denning, Janet Downie, Petr Dvorak, Karen D. Montgomery, Anis Feki, Angela Ford, Victoria Fox, Ana M. Fraga, Tzvia Frumkin, Lin Ge, Paul J. Gokhale, Tamar Golan-Lev, Hamid Gourabi, Michal Gropp, Lu Guangxiu, Ales Hampl, Katie Harron, Lyn Healy, Wishva Herath, Frida Holm, Outi Hovatta, Johan Hyllner, Maneesha S. Inamdar, Astrid Kresentia Irwanto, Tetsuya Ishii, Marisa Jaconi, Ying Jin, Susan Kimber, Sergey Kiselev, Barbara B. Knowles, Oded Kopper, Valeri Kukharenko, Anver Kuliev, Maria A. Lagarkova, Peter W. Laird, Majlinda Lako, Andrew L. Laslett, Neta Lavon, Dong Ryul Lee, Jeoung Eun Lee, Chunliang Li, Linda S. Lim, Tenneille E. Ludwig, Yu Ma, Edna Maltby, Ileana Mateizel, Yoav Mayshar, Maria Mileikovsky, Stephen L. Minger, Takamichi Miyazaki, Shin Yong Moon, Harry Moore, Christine Mummery, Andras Nagy, Norio Nakatsuji, Kavita Narwani, Steve K.W. Oh, Sun Kyung Oh, Cia Olson, Timo Otonkoski, Fei Pan, In Hyun Park, Steve Pells, Martin F. Pera, Lygia V. Pereira, Ouyang Qi, Grace Selva Raj, Benjamin Reubinoff, Alan Robins, Paul Robson, Janet Rossant, Ghasem H. Salekdeh, Thomas C. Schulz, Karen Sermon, Jameelah Sheik Mohamed, Hui Shen, Eric Sherrer, Kuldip Sidhu, Shirani Sivarajah, Heli Skottman, Claudia Spits, Glyn N. Stacey, Raimund Strehl, Nick Strelchenko, Hirofumi Suemori, Bowen Sun, Riitta Suuronen, Kazutoshi Takahashi, Timo Tuuri, Parvathy Venu, Yuri Verlinsky, Dorien Ward Van Oostwaard, Daniel J. Weisenberger, Yue Wu, Shinya Yamanaka, Lorraine Young, Qi Zhou

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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The International Stem Cell Initiative analyzed 125 human embryonic stem (ES) cell lines and 11 induced pluripotent stem (iPS) cell lines, from 38 laboratories worldwide, for genetic changes occurring during culture. Most lines were analyzed at an early and late passage. Single-nucleotide polymorphism (SNP) analysis revealed that they included representatives of most major ethnic groups. Most lines remained karyotypically normal, but there was a progressive tendency to acquire changes on prolonged culture, commonly affecting chromosomes 1, 12, 17 and 20. DNA methylation patterns changed haphazardly with no link to time in culture. Structural variants, determined from the SNP arrays, also appeared sporadically. No common variants related to culture were observed on chromosomes 1, 12 and 17, but a minimal amplicon in chromosome 20q11.21, including three genes expressed in human ES cells, ID1, BCL2L1 and HM13, occurred in >20% of the lines. Of these genes, BCL2L1 is a strong candidate for driving culture adaptation of ES cells.

Original languageAmerican English
Pages (from-to)1132-1144
Number of pages13
JournalNature Biotechnology
Issue number12
StatePublished - Dec 2011

Bibliographical note

Funding Information:
The International Stem Cell Initiative is funded by The International Stem Cell Forum. The authors would like to acknowledge the following: Medical Research Council, UK (P.W.A., H.M.); Mohammad Pakzad & Adeleh Taei, Royan Institute (H.B., G.H.S.); California Institute for Regenerative Medicine (CIRM) (E.C., P.W.L.); Institute of Medical Biology, A*STAR, Singapore (J.M.C.); Ministry of Education, Youth and Sports of the Czech Republic (P.D., A.H.); Stem Cell Research Center of the 21st Century Frontier Research Program, Ministry of Education, Science & Technology, Republic of Korea (SC-1140) (D.R.L., S.K.O.); Ministry of Science and Technology of China (863 program 2006AA02A102) (L.G.); Swedish Research Council, Cellartis (O.H.); Department of Biotechnology, Government of India, UK-India Education and Research Initiative and the Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India (M.I.); Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation, Leading Project of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) of the Japan Society for the Promotion of Science (JSPS), Grants in-Aid for Scientific Research of JSPS and MEXT (T.I., S.Y., K.T.); Swiss National Science Foundation (grant no. 4046-114410) (M.J.); Shanghai Science and Technology Developmental Foundation (06DJ14001), Chinese Ministry of Science and Technology (2007CB948004) (Y.J.); funding from the North West Science Fund, UK (S.K.); One North East Regional Developmental Agency, Medical Research Council, UK, Newcastle University (M.L.); research funding from the Australian Stem Cell Centre (A.L.L.); The Netherlands Proteomics Consortium grant T4-3 (C.M.); Stem Cell Network, Canada (A.N.); National BioResource Project, MEXT, Japan (N.N.); Singapore Stem Cell Consortium (SSCC) & the Agency for Science Technology and Research (A*STAR) (S.K.W.O., P.R.) and the Genome Institute of Singapore Core Genotyping Lab (P.R.); Academy of Finland, Sigrid Juselius Foundation (T.O.); Conselho Nacional de Desenvolvimento Científico e Tecnológico/Departamento de Ciência e Tecnologia do Ministério da Saúde (CNPq/MS/DECIT), and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (L.V.P.); supported by the kind donation of Judy and Sidney Swartz (B.R.); financial support from the Faculty of Medicine, University of New South Wales (UNSW) and the National Health and Medical Research Council (NHMRC) Program Grant no. 568969 (Perminder Sachdev), South Eastern Sydney and Illawarra Area Health Service (SEIAHS) for making hES cell line Endeavour-2 available for this study, and H. Chung and J. Kim for their help in preparing the samples (K.S.); Academy of Finland (grant 218050), the Competitive Research Funding of the Tampere University Hospital (grant 9F217) (H. Skottman).


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