Dec. 22, 2003 While the controversy surrounding the ethics of stem cell research shows no signs of abating, scientists continue to demonstrate the promise of stem cell–derived therapies for a wide range of degenerative diseases. The hope is that stem cells, which retain a unique "pluripotent" ability to morph into any of the 200 cell types of the human body, could be used to repair or replace damaged or diseased tissue. However, little is known about the molecular events that trigger this differentiation of stem cells. In this issue of PLoS Biology, Minoru Ko and colleagues present a model that takes a first step towards characterizing the molecular profile of stem cells, based on a comprehensive database of genes expressed in mouse early embryos and stem cells.
Arguing that a broad understanding of these molecular determinants requires a broad selection of cell types, the scientists combined new gene expression data on early embryos and stem cells with existing gene expression data to compare transcription patterns across a wide range of cell types and developmental stages. The expanded mouse transcriptome (record of transcribed genes) included data on unfertilized eggs; "totipotent" fertilized eggs, which have the potential to become any cell; pluripotent embryonic cells; various embryonic and adult stem cells; and fully differentiated cells.
Because they examined tissues that had not previously been included in studies of expressed sequences, Ko et al were able to find 1,000 new gene candidates, which they grouped according to particular embryonic stage and stem cell type. From these signature gene sets, they identified a cluster of 88 genes which may serve as molecular markers of developmental potential.
These results are consistent with previous findings that cells gradually lose developmental potential and that adult stem cells retain plasticity, but more importantly they link signature genes with different stem cell types and stages--thus providing a preliminary set of molecular markers for characterizing the function and potential of different stem cells. Identifying the genes that shape the unique properties of stem cells will shed light on the molecular pathways that guide development and suggest ways to best exploit the full therapeutic potential of these embattled cells.
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