The short answer is that we don't fully know what kicks most stem cells into action. Many adult stem cells seem to divide quite infrequently, just ticking over to keep their numbers constant. Even in tissues that are being constantly renewed, like the skin, most of the cell proliferation that produces the new specialized cells takes place among the immediate progeny of the stem cell. Not surprisingly, injury is one stimulus that can start stem cells producing specialized tissue cells for replacement.

It usually takes several cell divisions for the progeny of a stem cell to become fully differentiated cells. Along this line will be cells that can still give rise to several different cell types but have lost the ability to maintain a supply of unspecialized stem cells. Such cells are called progenitor cells. Whether to classify a cell as a stem cell or a progenitor has spurred many a squabble among scientists, largely because it's hard to determine experimentally exactly what these cells can do.

In some cases, the frequency with which stem cells throw off specialized cells seems to be guided by an internal 'clock', which might perhaps be tracking the number of times the stem cell has divided. But stem cells also take cues from their environment, such as the temperature, and whether they are attached to something or floating free. Most important, stem cells communicate with the other cells that surround them — the stem-cell niche. The cells send signals back and forth, and in some way we don't yet fully understand, the stem cells go where they need to go and become what they need to become, whether in the developing embryo or the adult. Whether researchers can provoke or mimic these signals sufficiently precisely to use stem cells for repairing the damage to tissues that occurs in neurodegenerative, cardiovascular and other diseases still remains to be seen.

Stem cell niches control whether, when, how, and in what directions stem cells divide. Scientists working to understand and reproduce niches in Petri dishes draw much of their language and theories from ecology.

Credit: Carol Marchetto and Fred H. Gage / The Salk Institute

Stem cell niches exist across plants and animals and are source of tissue repair and regeneration.