Conserved two-step regulatory mechanism of human epithelial differentiation

TY - JOUR

T1 - Conserved two-step regulatory mechanism of human epithelial differentiation

AU - Rane, Jayant K

AU - Droop, Alastair P

AU - Pellacani, Davide

AU - Polson, Euan S

AU - Simms, Matthew S

AU - Collins, Anne T

AU - Caves, Leo S D

AU - Maitland, Norman J

PY - 2014/2/11

Y1 - 2014/2/11

N2 - 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.

AB - 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.

U2 - 10.1016/j.stemcr.2014.01.001

DO - 10.1016/j.stemcr.2014.01.001

M3 - Article

C2 - 24527392

SN - 1550-8943

VL - 2

SP - 180

EP - 188

JO - Stem cell reviews and reports

JF - Stem cell reviews and reports

IS - 2

ER -