Ontology engineering

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volume 28 number 2 february 2010letters161 Expansion and maintenance of human embryonic stem cell–derived endothelialcells by TGFb inhibition is Id1 dependentD James, H-s Nam, M Seandel, D Nolan, T Janovitz, M Tomishima, L Studer, G Lee,D Lyden, R Benezra, N Zaninovic, Z Rosenwaks, S Y Rabbany & S Rafii167 Real-time imaging of hepatitis C virus infection using a fluorescent cell-basedreporter systemC T Jones, M T Catanese, L M J Law, S R Khetani, A J Syder, A Ploss, T S Oh,J W Schoggins, M R MacDonald, S N Bhatia & C M RiceEndothelial cells from hESCs, p 161172 Rational design of cationic lipids for siRNA deliveryS C Semple, A Akinc, J Chen, A P Sandhu, B L Mui, C K Cho, D W Y Sah,D Stebbing, E J Crosley, E Yaworski, I M Hafez, J R Dorkin, J Qin, K Lam,K G Rajeev, K F Wong, L B Jeffs, L Nechev, M L Eisenhardt, M Jayaraman,M Kazem, M A Maier, M Srinivasulu, M J Weinstein, Q Chen, R Alvarez, S A Barros,S De, S K Klimuk, T Borland, V Kosovrasti, W L Cantley, Y K Tam, M Manoharan,M A Ciufolini, M A Tracy, A de Fougerolles, I MacLachlan, P R Cullis, T D Madden &M J Hope178 CORRIGENDA AND ERRATA© 2010 Nature America, Inc. All rights reserved.Systematicly improving siRNA delivery,p 172careers and recruitment179 Fourth quarter lag in biotech hiringMichael Francisco180 peopleADVERTISEMENTBiotech in ChinaA special report analyzing China’s emerging biotech and pharmaceuticalindustries. The main feature investigates the local strategies of westernand Chinese organisations, assessing massive investment programs and areturning western trained skilled work force. Will China achieve its ambitionto develop and innovative drug discovery industry to compliment its genericsindustry? How long do the experts believe it will be before China has its ownhome grown innovative new drug approved for the global markets? What areactivities of western drug companies in China? The “Biotech in China” specialreport follows Letters on page 176 and is produced with the commercialsupport from the organizations featured in the Advertorial Partnering Profiles.nature biotechnologyv
in this issue© 2010 Nature America, Inc. All rights reserved.Endothelial cell recipeEndothelial cells derivedfrom pluripotent stem cellsmight one day provide theraw material for <strong>engineering</strong>or repairing blood vessels. Todevelop an improved methodfor vascular differentiation,Rafii and colleagues generatea human embryonic stemcell line that expresses greenfluorescent protein underthe control of the endothelialcell–specific VE-cadherinpromoter. Using this reportercell line to screen moleculesinvolved in early developmental signaling, they find thatinhibition of transforming growth factor (TGF)β beginning atday 7 of differentiation increases the yield of endothelial cellsand maintains the cells’ vascular phenotype for up to ten celldivisions. Mechanistic investigation identifies the transcriptionfactor Id1 as a key mediator of the effects of TGFβ inhibition.[Letters, p. 161]KAPredicting plant gene functionDespite extensive mutant screening,the functions of many plant genes arestill unknown. Lee et al. predict genefunction in the model plant Arabidopsisthaliana by gauging the likelihood thatpairs of genes are involved in the samebiological processes. Each pair of genesis assigned a score that combines manytypes of experimental and computationaldata gathered in Arabidopsis. Thescore also incorporates data from other organisms, such as yeast,worm, fly and humans, on genes that show substantial sequencesimilarity to Arabidopsis genes. Then, the function of an Arabidopsisgene is predicted based on the scores linking it to other genes withknown function. To demonstrate the utility of the approach, Lee etal. predicted and validated the roles of genes in seed pigmentation,lateral root development and drought sensitivity. By integrating multiplesources of data using methods customized for plants, Lee et al.predict gene function with greater confidence than by using only asingle source of data. This study provides a resource for identifyinggenes that influence agriculturally and economically important planttraits. [Resource, p. 149]CMWritten by Kathy Aschheim, Markus Elsner, Michael Francisco, Peter Hare,Craig Mak & Lisa MeltonPotent siRNA deliveryEmpirical screening has revealed novellipid nanoparticle formulations thathave substantially enhanced in vivodelivery of therapeutic small interfering(si)RNAs. Now Semple et al. haveset a new potency standard for siRNAdelivery to the liver by adopting a morerational approach to the design of cationic lipids. They refined anempirically identified cationic lipid (1,2-dilinoleyloxy-3-dimethylaminopropane),widely regarded as the benchmark for use inlipid nanoparticles, by dividing the structure into three functionalelements and then systematically testing modifications of each elementin isolation. This strategy to reveal structure-activity relationshipswas guided by the putative role of cone-shaped lipids to inducenonbilayer phases, such as the hexagonal H II phase illustrated here.When formulated to silence hepatic gene expression, the best-performinglipid variant conferred in vivo activity at siRNA doses aslow as 0.01 mg/kg in rodents and 0.1 mg/kg in nonhuman primates.[Letters, p. 172]PHLighting up HCV infectionProtocols for detecting hepatitis Cvirus infection without the need forcomplex manipulation of clinicalsamples or the use of genetically engineeredviruses is of prime importancefor many applications in basic researchand drug development. Rice and colleagueshave now developed a fluorescentreporter system that allows thedetection of individual cells infectedby wild-type viruses. The reportermolecule is based on a known target ofa viral protease, interferon-β promoterstimulator protein 1 (IPS-1). TheC-terminal part of IPS-1, includingthe mitochondrial targeting sequenceand the protease cleavage site, is fusedto a fluorescent protein and a nuclearlocalization sequence. Upon expressionof the viral protease the constructis cleaved and the fluorescentprotein relocalizes from the mitochondriato the nucleus. The authors usetheir reporter molecule to study viralpropagation in living cells and thedevelopment of stress responses in cells after infection. They alsodemonstrate that primary hepatocytes can be infected with hepatitisC viruses in vitro. [Letters, p. 167]MEnature biotechnology volume 28 number 2 february 2010v
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