OCT4 is enough for making hIPs cells

Human Embryonic Stem Cells double-stained with anti-Oct4 (green)
Human Embryonic Stem Cells double-stained with anti-Oct4 (green)

Earlier this year, the laboratory of Hans Schöler at the Max Planck Institute for Molecular Biomedicine in Münster (Germany), showed that only Oct4 was required to trigger the generation of induced pluripotent stem cells (iPS) from mouse adult neural stem cells. Yesterday, Nature published a report from his lab demonstrating that indeed OCT4 is the only factor required by human fetal neural stem cells to become pluripotent, to convert into iPS cells. Hans Schöler is one of the invited speakers at the next Transgenic Technology meeting, TT2010, that will be held in Berlin, March 22-24, 2010.

Shinya Yamanaka was the first identifying the “magic four” genes (OCT4, SOX2, c-MYC and KLF4) that were required to turn a somatic cell into an induced pluripotent stem (iPS) cell. His lab also showed later that only three were enough (OCT4, SOX2 and KLF4), discarding the c-MYC proto-oncogene that could cause tumours. The race towards the search for simpler reprogramming methods resulted in various papers showing that only two of these four initial factors were indeed required for triggering the generation of iPS cells. Hans Schöler demonstrated that OCT4, together with KLF4 or c-MYC, was sufficient to reprogram adult mouse neural stem cells into iPS cells. Douglas Melton obtained similar results with human fibroblasts using OCT4 and SOX2, in combination with a histone deacetylase inhibitor. Hans Schöler has now reduced the requirements to just one gene, OCT4, the only one that appears to be required to trigger pluripotency in human fetal neural stem cells.

The human stem cell image used in this post for illustrative purposes has been obtained from StemCellResources.org

2009 ISTT Elections for a Council Member

2009 ISTT elections for a council member
2009 ISTT elections for a council member

ISTT announces the 2009 Elections for a council member. The five nominated candidates are: Jan Ove Bratteng, Mary Ann Haskings, Aimee Stablewski, Marian van Roon and Elizabeth Williams. All ISTT members are invited to vote until September 22, through the ISTT Electronic Voting System, available at the elections section of the member’s area. Username and password required, automatic reminder available here.

VI Transgenic Animal Research Conference held in Tahoe

VI Transgenic Animal Research Conference, Lake Tahoe, CA, USA
VI Transgenic Animal Research Conference, Lake Tahoe, CA, USA

The VI Transgenic Animal Research Conference, organized by Jim Murray (UC Davis, CA, USA) has been held at the Granlibakken Conference Center, Tahoe City, Lake Tahoe, California, USA, August 17-21, 2009. The meeting has been co-sponsored by ISTT. Various ISTT members from different countries attended this very interesting international meeting, full of excellent talks and lively discussions.

At this conference, invited speakers have discussed about the latest technical developments and applications in animal transgenesis, including: ES and iPS cell isolation from non-murine animal species, the use of Zinc-Finger Nucleases to target animal genomes by standard microinjection, the use of transposons in transgenesis, antibody production in transgenic animals, knockout zebrafish and rats, biosafety assessment of transgenic large animals, environmental risk assessment of transgenic fish, risk analysis of transgene transfer in transgenic pigs during rearing, breeding and lactation; assessment of well-being and behavior of transgenic dairy goats, protein purification from the milk of transgenic animals, developing welfare protocols for transgenic large animals, oocyte production in zebrafish, xenotransplantation, regenerative medicine, degenerative and diabetes disease models in transgenic pigs, murine models of retinopathies, and the use of RNAi for disease resistance and modulation of production traits in transgenic chickens.

The invited speaker’s list included: Louis-Marie Houdebine, Stefan Moisyadi, Dan Carlson, Eric Shulze, Jorge Piedrahita, Paul Verma, Ning Li, Imre Kacskovics, Justin Jones, Eric Hallerman, Matthew Wheeler, Elizabeth Maga, Reinhard Huber, Cassandra Tucker, Bruce Draper, Andrew Wong, Scot Wolfe, Roland Buelow, Barbara Glenn, Lars Bolund, Eckhard Wolf, Peter Humphries, David Ayares, Heiner Niemann, Tim Doran and Robert Etches.

The last day of the meeting was devoted to a US-FDA/CVM workshop on the regulation of rDNA constructs in genetically engineered animals, with the presence of various delegates of the US-FDA/CVM.

Animal Biotechnology

Animal Biotechnology is an educational video, for outreach purposes, prepared by Alison L Van Eenennaam and colleagues of the Department of Animal Science, University of California, Davis, California, USA. This 30 min. video describes the development of various animal biotechnologies, including cloning and genetic engineering, and discusses both biomedical and agricultural applications addressing also some of the science-based and ethical concerns that are associated. The video includes the opinions and comments from leading academic and industry scientists in the field, conducted at the UC Davis Transgenic Animal Conference in 2007.

News on iPS cells research

mouse ES cells in culture
mouse ES cells in culture

Seven new papers have been released, as advanced publications, most recently in Nature, regarding the latest research on induced pluripotent stem (iPS) cells and three ISTT members are involved and co-author four of these manuscripts.

Two of these papers demonstrate the pluripotency of de novo created iPS cells since they can be used to generate adult fertile mice, using injection into or aggregation to tetraploid embryos. Sergey Kupriyanov (ISTT Ordinary member) co-authores one of these papers, from Kristin Baldwin’s laboratory at the Scripps Research Institute in La Jolla, CA, USA, whereas the other paper comes from Qi Zhou‘s laboratory (ISTT Honorary member), at the Chinese Academy of Sciences in Beijing, China, respectively.

Adult mice generated from induced pluripotent stem cells
Michael J. Boland, Jennifer L. Hazen, Kristopher L. Nazor, Alberto R. Rodriguez, Wesley Gifford, Greg Martin, Sergey Kupriyanov & Kristin K. Baldwin (doi:10.1038/nature08310) 2 August 2009

iPS cells produce viable mice through tetraploid complementation
Xiao-yang Zhao, Wei Li, Zhuo Lv, Lei Liu, Man Tong, Tang Hai, Jie Hao, Chang-long Guo, Qing-wen Ma, Liu Wang, Fanyi Zeng & Qi Zhou (doi:10.1038/nature08267) 23 July 2009

The five additional papers show, from different angles, that inactivating the tumor supressor gene p53 pathway, directly or indirectly, improves the efficiently of iPS cell production, suggesting that p53, besides its known role preventing tumorogenesis, would also be implicated in down regulating pluripotency of cells, thus preventing somatic cells to become pluripotent. This is a most interesting finding that links the biology of cancer cells and stem cells through a common mechanism, involving p53. Two of these papers, from Manuel Serrano’s and Maria Blasco’s laboratories, at the Spanish National Cancer Research Centre (CNIO) in Madrid, Spain, are co-authored by Sagrario Ortega (ISTT Ordinary member). Sagrario pioneered the use of iPS cells in Spain and gave a talk on this subject in the last TT2008 meeting, held in Toronto. The three remaining manuscripts come from the laboratories of Shina Yamanaka (Center for iPS Cell Research and Application (CiRA), Kyoto, Japan), Juan Carlos Izpisua-Belmonte (CRMB, Barcelona, Spain-Salk Institute, La Jolla, CA, USA) and Konrad Hochedlinger (Harvard Stem Cell Institute, Boston, MA, USA)

Suppression of induced pluripotent stem cell generation by the p53–p21 pathway
Hyenjong Hong, Kazutoshi Takahashi, Tomoko Ichisaka, Takashi Aoi, Osami Kanagawa, Masato Nakagawa, Keisuke Okita & Shinya Yamanaka (doi:10.1038/nature08235) 9 August 2009

Linking the p53 tumour suppressor pathway to somatic cell reprogramming
Teruhisa Kawamura, Jotaro Suzuki, Yunyuan V. Wang, Sergio Menendez, Laura Batlle Morera, Angel Raya, Geoffrey M. Wahl & Juan Carlos Izpisúa Belmonte (doi:10.1038/nature08311) 9 August 2009

The Ink4/Arf locus is a barrier for iPS cell reprogramming
Han Li, Manuel Collado, Aranzazu Villasante, Katerina Strati, Sagrario Ortega, Marta Cañamero, Maria A. Blasco & Manuel Serrano (doi:10.1038/nature08290) 9 August 2009

A p53-mediated DNA damage response limits reprogramming to ensure iPS cell genomic integrity
Rosa M. Marión, Katerina Strati, Han Li, Matilde Murga, Raquel Blanco, Sagrario Ortega, Oscar Fernandez-Capetillo, Manuel Serrano & Maria A. Blasco (doi:10.1038/nature08287) 9 August 2009

Immortalization eliminates a roadblock during cellular reprogramming into iPS cells
Jochen Utikal, Jose M. Polo, Matthias Stadtfeld, Nimet Maherali, Warakorn Kulalert, Ryan M. Walsh, Adam Khalil, James G. Rheinwald & Konrad Hochedlinger (doi:10.1038/nature08285) 9 August 2009