Integration of Stemness Gene Signatures Reveals Core Functional Modules of Stem Cells and Potential Novel Stemness Genes

Abstract

Stem cells encompass a variety of different cell types which converge on the dual capacity to self-renew and differentiate into one or more lineages. These characteristic features are key for the involvement of stem cells in crucial biological processes such as development and ageing. To decipher their underlying genetic substrate, it is important to identify so-called stemness genes that are common to different stem cell types and are consistently identified across different studies. In this meta-analysis, 21 individual stemness signatures for humans and another 21 for mice, obtained from a variety of stem cell types and experimental techniques, were compared. Although we observed biological and experimental variability, a highly significant overlap between gene signatures was identified. This enabled us to define integrated stemness signatures (ISSs) comprised of genes frequently occurring among individual stemness signatures. Such integrated signatures help to exclude false positives that can compromise individual studies and can provide a more robust basis for investigation. To gain further insights into the relevance of ISSs, their genes were functionally annotated and connected within a molecular interaction network. Most importantly, the present analysis points to the potential roles of several less well-studied genes in stemness and thus provides promising candidates for further experimental validation.