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Forced expression of proneural transcription factors has been shown to direct neuronal conversion of fibroblasts. Because neurons are postmitotic, conversion efficiencies are an important parameter for this process. We present a minimalist approach combining two-factor neuronal programming with small molecule-based inhibition of glycogen synthase kinase-3β and SMAD signaling, which converts postnatal human fibroblasts into functional neuron-like cells with yields up to >200% and neuronal purities up to >80%.

The biomedical application of human embryonic stem (hES) cells will increasingly depend on the availability of technologies for highly controlled genetic modification. In mouse genetics, conditional mutagenesis using site-specific recombinases has become an invaluable tool for gain- and loss-of-function studies. Here we report highly efficient Cre-mediated recombination of a chromosomally integrated loxP-modified allele in hES cells and hES cell-derived neural precursors by protein transduction. Recombinant modified Cre recombinase protein translocates into the cytoplasm and nucleus of hES cells and subsequently induces recombination in virtually 100% of the cells. Cre-transduced hES cells maintain the expression of pluripotency markers as well as the capability of differentiating into derivatives of all three germ layers in vitro and in vivo. We expect this technology to provide an important technical basis for analyzing complex genetic networks underlying human development as well as generating highly purified, transplantable hES cell-derived cells for regenerative medicine.

Recent new technologies enabling the genetic modification of human embryonic stem cells and the derivation of patient-specific induced pluripotent stem cells provide attractive opportunities for the development of new cell-based bioassays. Both technologies critically depend on the selection of pluripotent cell colonies. AVISO's CellCelector™ enables automated colony detection and collection, thereby bypassing tedious manual selection procedures.

Clonal analysis represents the gold standard for assaying the differentiation potential of stem cells in vitro. Here we describe Elektra™, a system that permits efficient spotting of single cell clones in a coculture paradigm. Joining their expertise, Evotec Technologies and LIFE & BRAIN showed that neural precursors derived from human embryonic stem (ES) cells survive single cell spotting and continue to generate individual clones. This technology should be particularly useful for the high-throughput clonal analyses increasingly required for human stem cell applications.

In pharmaceutical screening and cell biology research, the availability of cells can become a bottleneck in the logistic chain of experiments. Hamilton and Life & Brain have joined their expertise to develop a fully automated system for the culture of primary cells, cell lines and embryonic stem (ES) cells, which provides high-quality cells in large numbers.