Wednesday, 29 June 2011

Molecular Cartography for Stem Cells

From Cell

Researchers have long suspected that cancer cells and stem cells share a core molecular signature, but this commonality remains incompletely understood. By examining microRNA (miRNA) expression patterns in multiple types of cancer cells and stem cells, Neveu et al. (2010) have now developed the miRMap, a tool that facilitates quantitative examination of the molecular hallmarks associated with a cell's identity. Their effort resulted in a catalog of expression patterns for nearly 330 miRNAs in over 50 different human cell lines. Despite the overwhelming molecular heterogeneity among the samples, their analysis identifies 11 miRNAs that comprise a signature common to all cancer cells and shared by a subset of pluripotent stem cells. The genes targeted by these miRNAs downregulate cell proliferation or upregulate the p53 network. Although recent reports have called attention to the inherent oncogenic risk of stem cells, this new study shows that only some pluripotent stem cells look like cancer cells, and this cancer-like state cannot be predicted by a stem cell's tissue of origin or method of production. By examining the changes associated with cellular reprogramming—both when stem cells are generated from somatic cells and when induced pluripotent stem cells (iPSCs) are differentiated—Neveu et al. reveal a precise window for cancer-like behavior during iPSC generation, emphasizing that a transient downregulation of p53, rather than a complete inhibition, is required to fully reprogram somatic cells into pluripotent stem cells. Multidimensional molecular maps, such as the miRMap, help us draw a more complete picture of the events that drive the acquisition of specific cell fates during cellular reprogramming.

P. Neveu et al. (2010). Cell Stem Cell 7, 671–681.

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