Press releases
Please quote Nature Biotechnology as the source of these items.
The January 2008 issue of Nature Biotechnology is available online.
January 2008
Induced pluripotent stem cells without tumors
Building on their research reported last week, Shinya Yamanaka and colleagues show how to convert adult mouse or human skin cells into cells that resemble embryonic stem cells without using the tumor-causing gene c-Myc. The paper will be published online in Nature Biotechnology. Elimination of c-Myc is considered a critical step in making these so-called 'reprogrammed' cells safe for clinical applications in patients.
As originally described, the reprogramming method works by introducing four specific genes into skin cells and identifying the rare cells, known as induced pluripotent stem (iPS) cells, that acquire properties of pluripotency—the ability to become any specialized cell of the body. The method was demonstrated by Yamanaka's group in publications in 2006 and 2007 using cells from mice. Last week, two papers reported success with human cells. However, one of these papers—also from Yamanaka's group—used the c-Myc gene, which makes iPS cells prone to form tumors, and the other one—from a US team—used fetal and neonatal cells rather than adult cells.
The authors demonstrate the generation of iPS cells from adult mouse and human skin cells with only three genes, not including c-Myc. To determine whether the absence of c-Myc reduces the propensity to form tumors, the authors studied mouse iPS cells in a rigorous test that involves generating 'chimeric' mice harboring many specialized cells derived from the iPS cells. None of the 26 animals derived from iPS cells without c-Myc died of tumors (at the last, 100-day time point), whereas 6 of 37 animals from iPS cells with c-Myc did, showing that the absence of c-Myc reduces tumor incidence.
The human skin cells reprogrammed in the present study came from a 36-year-old adult. Reprogramming adult cells may be more clinically relevant than reprogramming neonatal cells as in principle it would make patient-specific pluripotent cells available to adults for use in cell-replacement therapies.
Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts pp 101 - 106
Masato Nakagawa, Michiyo Koyanagi, Koji Tanabe, Kazutoshi Takahashi, Tomoko Ichisaka, Takashi Aoi, Keisuke Okita, Yuji Mochiduki, Nanako Takizawa & Shinya Yamanaka
Published online: 30 November 2007 | doi 10.1038/nbt1374
Anatomy of a pandemic flu threat
Widespread transmission of bird flu between humans would require the virus to develop the ability to recognize umbrella-shaped structures in the human respiratory tract. This finding, reported online this week in Nature Biotechnology, promises to change how scientists monitor human adaptation of flu viruses and how doctors diagnose and treat both seasonal influenza and a potential H5N1 pandemic.
Most human flu pandemics are thought to have arisen from mutant viruses that combine features of both animal and human influenzas, but knowing exactly what to look for when analyzing new variants is key to anticipating an outbreak. Flu viruses attack by binding sugar chains that line the airways and lungs. The chemical linkages between the sugar molecules in these chains differ between humans and birds, and until now it has been assumed that bird flu viruses adapt to humans simply by acquiring mutations that enable them to attach to human sugar linkages.
Ram Sasisekharan and colleagues show that human adaptation depends on the shape assumed by the flexible sugar chains rather than the type of linkage. Bird flu viruses currently require cone-shaped sugar chains to infect birds, so the umbrella shape found in humans has protected most of us from avian flu. One implication of this finding is that bird flu strains that might have triggered alarm may not be a cause for undue concern provided that they cannot bind umbrella-shaped sugar chains.
Glycan topology determines human adaptation of avian H5N1 virus hemagglutinin pp 107 - 113
Aarthi Chandrasekaran, Aravind Srinivasan, Rahul Raman, Karthik Viswanathan, S Raguram, Terrence M Tumpey, V Sasisekharan & Ram Sasisekharan
Published online: 6 January 2008 | doi 10.1038/nbt1375