Cancer stem cells and embryonic stem cells are both able to renew themselves indefinitely, but whether they share a common pathway of 'stemness' has remained controversial. To investigate just how closely related they are, Howard Chang and his team at Stanford University, California, have devised a method of mapping the genetic fingerprints of both these cell types. They have found a set of gene-expression programs used by both embryonic stem cells and many aggressive human cancers, which may have significant implications for cancer diagnosis and therapeutics1.

To get as complete a picture as possible of the gene-expression profiles of embryonic stem (ES) cells and a variety of different adult stem cells, the researchers integrated hundreds of mouse stem cell microarray data sets and other gene-expression data from several independent studies. “We wanted to understand stemness at a molecular level,” says Chang. Instead of just showing which individual genes are switched on or off, they created a 'module map' that shows transcriptional programs in terms of sets, or modules, of genes that act together to perform a specific function. The stem cells they examined fell into two groups: one that showed an ES cell-like pattern of gene expression and included retinal stem cells and fetal liver cells; and another that included bone marrow stem cells and mammary stem cells from adult tissues and, surprisingly, had its own distinctive profile.

Having characterized an ES cell-like module of gene expression, the group examined the expression profiles of a variety of human cancers and observed that diverse cancers shared the ES cell-like module, which was also highly indicative of a poor prognosis. “The next question was: What would happen if we switched on the ES cell-like program? Would it bring out features similar to cancer stem cells?” asks Chang. The group found that a single gene, c-Myc, seemed to be responsible for activating the ES cell-like transcriptional program in the tumour cells. They established that turning on the ES cell-like program in both transformed mouse epidermal cells and human epithelial cancer cells directly induces so-called 'cancer stem cells', which are able to initiate and maintain tumours. c-Myc expression also seems to be key in activating the transcriptional program of the ES cell-like group of normal tissue stem cells identified in the first part of the study.

One of the most interesting conclusions of the study is that there is clearly no single 'stemness' program shared by all stem cells. Instead, it seems that only some groups of non-embryonic stem cells share a core transcriptional program with ES cells, a view agreed with in a more recent Nature Genetics paper2 from Robert Weinberg's group at the Massachusetts Institute of Technology, in Cambridge. In addition, understanding better why some tumour cells express this ES cell-like gene module will allow the production of uniform tumour cells for research. “Cancer stem cells are rare,” says Chang. “Being able to make them in a lab will be very useful to study their biology and work out why, despite similar transcriptional programs, they function differently from ES cells.”

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