Modern genome-wide genetic approaches to reveal intrinsic properties of stem cells

Purpose of review The clinical use of hematopoietic stem cells, which produce all mature blood cell lineages in the circulation, is continuously increasing. Identification of genes and gene networks specifying either sternness or commitment will not only be of major relevance for a fundamental understanding of developmental biology, but also for the emerging fields of tissue engineering and regenerative medicine. Our appreciation of the transcriptional machinery that distinguishes stem cells from their nonstem cell progeny is, however, rudimentary. State-of-the art genome-wide tools are now becoming available to elucidate intrinsic properties of stem cells. Here, we review recent progress that has been made in this field. Recent findings Approaches to study stem cell-specific genes and gene networks include genetical genomics, mRNA and microRNA expression profiling of carefully selected cells, proteomics, chromatin studies using 'CHIP-on-chip' tools, genome-wide binding site analyses for transcription factors and chromatin-remodeling proteins, and tools to study the three-dimensional organization of gene loci. It is promising to see that the combined application of these tools has resulted in the identification of multiple novel genes that regulate stem cell self-renewal. Summary Exploitation of the available technology and integrating the data by translation into a dynamic model of networks, operating in all four dimensions, will be essential to fully comprehend the elusive concept of 'stemness'. It is time to harvest