Adult stem cells have been suspected of retaining developmental preferences, that is, a tendency to revert to type. For example, stem cells originally derived from skin would be biased toward developing into skin cells again, and the same for blood cells or cells of any other type. Although this cell-level developmental preference has been given a name—epigenetic memory—whether it actually exists has remained an open question. A new study, however, suggests that the idea of epigenetic memory may need to be forgotten.
Researchers from the University of Helsinki compared the characteristics of induced pluripotent stem cells (iPSCs) derived from skin to those derived from blood using a comprehensive range of analytical methods. In addition to gene expression, they studied DNA methylation and the spontaneous and guided differentiation capacity of the stem cells. The results were unambiguous: several different indicators showed that the type of original cell made no difference when the stem cell was fully reprogrammed.
The researchers’ work appeared January 14 in the journal Stem Cell Reports in an article entitled “Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential.” The article explained that fibroblasts and blood cells were used because those tissues are of the most practical relevance for biobanking. Blood cells are particularly useful as biobank material because taking blood samples is a simple process, routinely done in the course of diagnostics and treatment.
“Our results show that iPSC lines derived from the same donor are highly similar to each other,” wrote the article’s authors. “However, genetic variation imparts a donor-specific expression and methylation profile in reprogrammed cells that leads to variable functional capacities of iPSC lines.”
The second observation—that donor genotype shapes the differentiation behavior of the stem cell—was particularly striking. In fact, the University of Helsinki researchers noted that the impact of donor variability far exceeds source-cell-specific differences in iPSC lines.
Both findings from the current study have direct practical relevance to biobanking. “Our results suggest that integration-free, bona fide iPSC lines from fibroblasts and blood can be combined in repositories to form biobanks,” the authors concluded. “Due to the impact of genetic variation on iPSC differentiation, biobanks should contain cells from large numbers of donors.”
“The genetically determined individual differences in stem cell differentiation were surprisingly extensive,” explained Professor Timo Otonkoski from the University of Helsinki. “This means that to make reliable observations about the functional implications of genotypes related to an illness requires that biobanks acquire a sufficiently large variety of samples from several donors.”
“It is obvious that pluripotent stem cells derived from different cell types are fully equal,” he continued. “These results are highly significant to biobanks, as this way one collection can feature different source cells, and previously stored living cell samples remain useful for iPSC production.”