conserved two-step regulatory mechanism of human epithelial differentiation

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ID: 233093
2014
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Abstract
Human epithelia are organized in a hierarchical structure, where stem cells generate terminally differentiated cells via intermediate progenitors. This two-step differentiation process is conserved in all tissues, but it is not known whether a common gene set contributes to its regulation. Here, we show that retinoic acid (RA) regulates early human prostate epithelial differentiation by activating a tightly coexpressed set of 80 genes (e.g., TMPRSS2). Response kinetics suggested that some of these genes could be direct RA targets, whereas others are probably responding indirectly to RA stimulation. Comparative bioinformatic analyses of published tissue-specific microarrays and a large-scale transcriptomic data set revealed that these 80 genes are not only RA responsive but also significantly coexpressed in many human cell systems. The same gene set preferentially responds to androgens during terminal prostate epithelial differentiation, implying a cell-type-dependent interplay between RA and tissue-specific transcription factor-mediated signaling in regulating the two steps of epithelial differentiation.
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rane2014stemconserved Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Jayant K. Rane;Alastair P. Droop;Davide Pellacani;Euan S. Polson;Matthew S. Simms;Anne T. Collins;Leo S.D. Caves;Norman J. Maitland
Journal nature reviews gastroenterology & hepatology
Year 2014
DOI
10.1016/j.stemcr.2014.01.001
URL
http://www.sciencedirect.com/science/article/pii/S2213671114000022
Keywords
medicine (general)biology (general)

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