Creating a blood line from human skin

The possibility of reprogramming somatic cells into pluripotent stem cells by defined sets of transcription factors, which has been delineated in landmark discoveries over the past few years [1], has removed a major roadblock to stem cell applications. The ability to generate patient-specific stem cells by this method has greatly extended the potential for autologous stem cell therapy and cell culture models of specific diseases. As with embryonic stem cells, however, these strategies still depend on complex differentiation protocols to derive mature cells of a defined specificity, a task that is often hindered by our limited understanding of cell fate determination. For practical applications, any residual cells escaping a differentiation stimulus engender a high risk of tumor formation in vivo, as pluripotent stem cells are tumorigenic. In addition, differentiation protocols might yield cell types that are close, but not identical, to the required mature cells. For example, hematopoietic differentiation of pluripotent stem cells typically gives rise to red blood cells expressing embryonic globin genes, and it has proved more difficult to induce expression of the adult genes.A recent series of papers has explored a short cut - the direct conversion of fibroblasts into differentiated cell types of other lineages, such as macrophage-like cells [2], neurons [3] or cardiomyocytes [4], without prior generation of pluripotent stem cells. This is typically achieved by the expression of transcription factors implicated in the developmental program of the desired lineage. These studies used mouse fibroblasts, but a paper published recently in Nature by Mick Bhatia and colleagues (Szabo et al. [5]) shows that direct lineage conversion is also possible in human cells. The authors obtained hematopoietic cells with multilineage potential by the ectopic expression of the transcription factor OCT4 in both neonatal and adult human fibroblasts. Interestingly, lineage conversion did