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Gene Expression Profile Created for Mouse Stem Cells and Developing Embryo

Gene Expression Profile Created for Mouse Stem Cells and Developing Embryo


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. Many animal studies have supported this potential for both embryonic and adult stem cells, with some findings indicating that hematopoietic (blood-forming) stem cells could be cultured and used to help cancer patients who need bone-marrow transplants, and others suggesting that adult brain stem cells could repair damaged nerve tissue and help paralysis patients recover movement.

Despite these advances, little is known about the molecular events that trigger differentiation and determine a cell's developmental potential. Such information will help scientists better manipulate this potential in stem-cell therapies. Having compiled a comprehensive database of genes expressed in mouse early embryos and stem cells, Minoru Ko and colleagues present a model that takes the first step toward characterizing the molecular profile of 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.

Ko et al. characterized gene activity in this diverse cross-section of cells and looked for molecular differences, including the level and type of gene expression, as a measure of developmental potential. Applying standard statistical tools to spot major trends and clusters in gene expression, the researchers found 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 whose average expression level decreased as cells became more specialized. This finding indicates not only that totipotent and pluripotent cells have distinct genetic profiles, but that these 88 genes may serve as molecular markers of developmental potential. Further support of this predictive power comes from the finding that adult stem cells—cells derived from adult organs that retain a measure of pluripotency—were clustered with early embryonic tissues of similar 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.