Adult stem cells represent a sort of blank clay from which a myriad of different cell and tissue types are molded and as such are of critical importance to health, ageing and disease. In tissues that turn over rapidly, such as the intestines, the self-renewing nature of stem cells and their susceptibility to cancer-causing mutations has led researchers to postulate that these cells also act as the cell of origin in cancers. The rarity of adult stem cells relative to their differentiated daughter cells has, however, made them historically difficult to study.
Over the years, researchers have hypothesized that the body maintains a population of mutation- and injury-resistant “reserve” stems cells that serve as a kind of dormant reservoir from which all other cells in a given tissue can be derived. Yet researchers have been conflicted about the precise identity of this population of cells.
Now, a team from the University of Pennsylvania has helped identify key characteristics that distinguish reserve stem cells from other stem cell populations that had been purported to have similar properties. The work, which employed single-cell gene expression analyses as well as other cutting-edge techniques, demonstrated that, in the intestines, reserve stem cells are a distinct population from so-called “label-retaining cells.” The two populations were long believed to be one and the same.
“The devil is in the details,” said senior author Christopher J. Lengner, an assistant professor in the Department of Biomedical Sciences in Penn’sSchool of Veterinary Medicine and member of the Penn Institute for Regenerative Medicine. “You need an assay with single-cell sensitivity to address the potential heterogeneity in the cell population being study and thus to truly understand what these cells are. Now that we have that level of resolution, we can begin to ask questions that are relevant to questions such as how cancer is initiated, a process that starts in a single cell.”
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The paper appears in the journal Gastroenterology.