To test for coordinate regulation of gene homologs or modules across different stem cell types, we developed a pattern recognition algorithm capable of combining the results of any number of experiments to identify significantly and recurrently up- or down-regulated genes and gene modules in stem cells. To obtain a global overview of stem cell expression patterns, we assembled a compendium of data from 30 different studies assaying gene expression of 49 stem cell populations representing twelve different types of stem cells including hematopoietic, retinal, neural, embryonic, and intestinal. From each of the 49 datasets we collected genes up-regulated in stem cells into a stem cell gene list and, where available, a corresponding set of genes up-regulated in differentiated cells into a differentiated gene list. The use of gene lists facilitated the straightforward integration of results from the variety of experimental test platforms, which has proven effective for meta-analysis compared to alternative approaches. A permissive, or poised, chromatin structure may underlie stem cell multipotency. S-MAP detected several chromatin-related modules Tulathromycin B associated with stemness including those involved in imprinting, chromatin-dependent silencing, heterochromatin and the nuclear lamina, which may indicate widespread suppression of lineage-associated genes. Stemness contributors include the Chd/Smarca family, nucleosome assembly protein like proteins; and histone variants H2afz and H2afv. Indeed, Chd1 was recently shown to be important in ESC multipotency by regulating chromatin structure; other Amikacin hydrate family members may fill this function in adult stem cells. S-MAP also revealed a number of Wnt signaling modules with alternating patterns of specificity in different stem cell types. Wnt-related stemness modules include the secreted Frizzled-like proteins of the Sfrp family; the Frizzled receptors; a subfamily of the TCF/LEF transcriptional regulators; the Enhancer of Split/Groucho-related Tle factors; and both alpha- and delta-catenins. Whether Wnt signaling regulates stem cell maintenance or differentiation has been extensively debated, and some genes have both inhibitory and activating abilities dependent on the state of Wnt signals. While functional consequences cannot be resolved by expression data alone, our analysis demonstrates that all stem cells tightly regulate the Wnt pathway at the transcriptional level. The identified S-MAP patterns provide specific candidates for functional interrogation in different stem cell types. DNA repair is uniquely critical in stem cells as mutations accumulated in stem cells amplify in differentiated daughters. SMAP identified many stemness modules associated with DNA repair, including the Terf, p53, and Rad families. Terf1 and 2 are highly stem cell-specific and are expressed in alternating patterns in different stem cells. S-MAP classified the p53 family as a stemness-on module. While p53 was found to be expressed in several tissues, p63 was upregulated in gastric and intestinal cells consistent with its known role in the development and maintenance of epithelial stem cells. Likewise, Brca1 and its homolog Mcph1, the Msh family of proteins, and a Rad/Dmc module were detected as stemness modules by S-MAP. Several transcriptional regulators, including the Myb family of oncogenes, were among the highest scoring stemness-on modules. c-myb was enriched in hematopoietic stem cells, consistent with its known role in differentiation control, as well as neural, embryonic, 
intestinal and retinal stem cells. a-myb complements the expression of its partner genes by significant upregulation in gastric stem cells, while b-myb was up-regulated in liver and trophoblast stem cells. The Pbx and Id families have also been implicated in maintaining stem cell function. The myc family displayed a strongly complementary stemness expression pattern. c-myc has been implicated in reprogramming of differentiated cells into pluripotent cells.