Diverse Adult Stem Cells Share Specific Higher-Order Patterns of Gene Expression

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Abstract
Adult tissue stem cells (SCs) share functional properties regardless of their tissue of residence. It had been thought that SCs might also share expression of certain “stemness” genes, although early investigations for such genes were unsuccessful. Here, we show that SCs from diverse tissues do preferentially express certain types of genes and that SCs resemble other SCs in terms of global gene expression more than they resemble the differentiated cells (DCs) of the tissues that they supply. Genes associated with nuclear function and RNA binding were over-represented in SCs. In contrast, DCs from diverse tissues shared enrichment in genes associated with extracellular space, signal transduction, and the plasma membrane. Further analysis showed that transit-amplifying cells could be distinguished from both SCs and DCs by heightened expression of cell division and DNA repair genes and decreased expression of apoptosis-related genes. This transit-amplifying cell-specific signature was confirmed by de novo generation of a global expression profile of a cell population highly enriched for transit-amplifying cells: colonic crypt-base columnar cells responding to mucosal injury. Thus, progenitor cells preferentially express intracellular or biosynthetic genes, and differentiation correlates with increased expression of genes for interacting with other cells or the microenvironment. The higher-order, Gene Ontology term-based analysis we use to distinguish SC- and DC-associated gene expression patterns can also be used to identify intermediate differentiation states (e.g., that of transit-amplifying cells) and, potentially, any biological state that is reflected in changes in global gene expression patterns. Disclosure of potential conflicts of interest is found at the end of this article.