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

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

Genomic engineering of the cystic fibrosis gene in patient-derived iPS cells

Resumen del póster presentado en el "Collaborative Congress of the European Society for Gene and Cell Therapy and the Spanish Society for Gene and Cell Therapy" celebrado del 25 al 28 de octubre de 2013 en Madrid (España)Peer reviewe

Targeting HIV entry through interaction with envelope glycoprotein 120 (gp120): Synthesis and antiviral evaluation of 1,3,5-triazines with aromatic amino acids

On the basis of the interesting inhibitory properties that lectins show against HIV-replication through their interaction with glycoprotein 120 (gp120), we here describe the design, synthesis, and anti-HIV evaluation of three series of 1,3,5-triazine derivatives (monomers, dimers, and trimers) functionalized with aromatic amino acids meant to mimic interactions that lectins establish with gp120. While monomers were inactive against HIV replication, dimers showed limited anti-HIV activity that is, however, considerably more significant in the trimers series, with EC50 values in the lower μM range. These findings most likely reflect the requirement of multivalency of the 1,3,5-triazine derivatives to display anti-HIV activity, as lectins do. The pronounced anti-HIV activity (EC50 ∼ 20 μM) is accompanied by the absence of toxicity in CEM T-cell line (CC50 > 250 μM). Moreover, SPR experiments revealed that the prototype trimers with a central core of 2,4,6-triethylbenzene and six l-Trp or six l-Tyr residues at the periphery were efficient binders of CXCR4- and CCR5-tropic HIV-1 gp120 (estimated KD: lower micromolar range). The collected data support the interest of this novel family of anti-HIV agents and qualify them as potential novel microbicide lead compounds.V.L. thanks CSIC and the Fondo Social Europeo (FSE) for an I3P predoctoral contract.We thank María Nares and Leen Ingels for excellent technical assistance. Financial support to M. Nares by the Spanish MEC and the FSE is gratefully acknowledged. This work has been supported by a grant of the Spanish CICYT (SAF2009-13914-C02-01), the CSIC (PIF Programme ref LECTIVIR PIF08-022), the KU Leuven (GOA no. 10/014; EF 05/ 15; PF 10/018), the European Commission (CHAARM) and the FWO-Vlaanderen (no. G.485.08).Peer Reviewe

Structure-Activity relationship studies on a TPR dendrimer with dual activities against HIV and enterovirus A71. Modifications on the amino acid

We have recently described a new class of dendrimers with tryptophan (Trp) on the surface that show dual antiviral activities against HIV and EV71 enterovirus. The prototype compound of this family is a pentaerythritol derivative with 12 Trps on the periphery. Here we complete the structure-activity relationship studies of this family to identify key features that might be significant for the antiviral activity. With this aim, novel dendrimers containing different amino acids (aromatic and non-aromatic), tryptamine (a “decarboxylated” analogue of Trp) and N-methyl Trp on the periphery have been prepared. Dendrimer with N-Methyl Trp was the most active against HIV-1 and HIV-2 while dendrimer with tyrosine was endowed with the most potent antiviral activity against EV71. This tyrosine dendrimer proved to inhibit a large panel of EV71 clinical isolates (belonging to different clusters) in the low nanomolar/high picomolar range. In addition, a new synthetic procedure (convergent approach) has been developed for the synthesis of the prototype and some other dendrimers. This convergent approach proved more efficient (higher yields, easier purification) than the divergent approach previously reported.Ministerio de Economía, Comercio y Empresa (España)KU LeuvenBelgian Interuniversity Attraction PolesChina Scholarship CouncilDepto. de Química en Ciencias FarmacéuticasFac. de FarmaciaTRUEpu