Transcriptome-wide noise controls lineage choice in mammalian progenitor cells

Hannah H. Chang, Martin Hemberg, Mauricio Barahona, Donald E. Ingber and Sui Huang ()
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Hannah H. Chang: Vascular Biology Programme, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
Martin Hemberg: Imperial College London, South Kensington Campus
Mauricio Barahona: Imperial College London, South Kensington Campus
Donald E. Ingber: Vascular Biology Programme, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
Sui Huang: Vascular Biology Programme, Children’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA

Nature, 2008, vol. 453, issue 7194, 544-547

Abstract: Pluripotency: Cell-to-cell variations Even in clonal populations of cells, there is significant phenotypic variation from cell to cell. This could reflect the 'noise' inherent in gene expression: or the various cell states could represent stable phenotypic variants. Chang et al. analysed the behaviour of an 'outlier' in clonal populations of mouse haematoipoietic stem cells that had very high expressions of the stem cell marker Sca-1 and found that outliers possessed distinct transcriptomes. Though the transcriptomes eventually reverted back to that of the median cells, while they differed they could drive the cells to express characteristics of distinct cell fates. Thus clonal heterogeneity of gene expression may not be due to noise in the expression of individual genes, but rather is a manifestation of metastable states of a slowly fluctuating transcriptome. These fluctuations may govern the reversible, stochastic priming of multipotent progenitor cells in cell fate decision.

Date: 2008
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DOI: 10.1038/nature06965

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