Nature Journal Club

Michael K. Richardson

Leiden University, the Netherlands

A developmental biologist highlights potential pitfalls of using stem cells that can ‘remember’ their origins.

For me, embryos are beautiful and their development is endlessly fascinating. They are experts at making new tissues, and accomplish this by using stem cells. Stem cells can develop into mature tissues such as bone or muscle; but, cleverly, some of their progeny remain in an undeveloped state, forming reserve supplies that remain in our bodies into adulthood.

Adult stem cells are found in tissues where cell populations are constantly being renewed, such as the testes, hair follicles and bones. We replace our entire skeleton every decade or so, and rely on stem cells in our bones to do this. Stem cells also have an important role in repair, swinging into action to deal with broken bones and other mishaps.

A recent study in mice yielded remarkable evidence that some of these adult stem cells remember where in the embryo they came from. Jill Helms and her colleagues at Stanford University in California grafted stem cells from one bone into another to see whether they would help repair fractures in the ‘wrong’ location. Stem cells transplanted from leg bones into fractured jaws failed to produce new bone (P. Leucht et al. Development 135, 2845–2854; 2008). Interestingly, the uncooperative stem cells continued to express a gene, Hoxa11, that acts as a kind of embryonic ‘postcode’ for the leg.

These findings have broad implications. They validate the concept of non-equivalence — that seemingly identical cells differ if they come from different places in the embryo — first enunciated by Julian Lewis and Lewis Wolpert in the 1970s, and show that it holds in the adult. More pragmatically, if some stem cells also have positional memory, doctors may need to make sure that they take stem cells from the right location to heal damaged tissues.

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