Intestinal Stem Cell Replacement Follows a Pattern of Neutral Drift

• Published in: Science (American Association for the Advancement of Science) Vol. 330; no. 6005; pp. 822 - 825
• Main Authors: Lopez-Garcia, Carlos, Klein, Allon M, Simons, Benjamin D, Winton, Douglas J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 05.11.2010; The American Association for the Advancement of Science
• Subjects: analytical methods; Animals; Biological and medical sciences; Cell Differentiation; Cell Division; Cell growth; Cell Lineage; Cellular biology; Clone Cells - cytology; clones; Colon; Colon - cytology; Contracts; Crypts; Digestive system; Division; Drift; Dynamic tests; Dynamical systems; Dynamics; Epithelial cells; Fundamental and applied biological sciences. Psychology; Genetics; Goblets; Homeostasis; intestinal mucosa; Intestinal Mucosa - cytology; Intestine, Small - cytology; Legends; Mice; physics; Population (statistical); population dynamics; Research fellowships; Size distribution; Stem cells; Stem Cells - cytology; Stem Cells - physiology; Vertebrates: nervous system and sense organs; Regeneration; Cell death; Stem cell; Distribution; Turnover; Cell division; Homeostasis; Behavior; Long term
• ISSN: 0036-8075; 1095-9203; 1095-9203
• DOI: 10.1126/science.1196236

With the capacity for rapid self-renewal and regeneration, the intestinal epithelium is stereotypical of stem cell-supported tissues. Yet the pattern of stem cell turnover remains in question. Applying analytical methods from population dynamics and statistical physics to an inducible genetic labeling system, we showed that clone size distributions conform to a distinctive scaling behavior at short times. This result demonstrates that intestinal stem cells form an equipotent population in which the loss of a stem cell is compensated by the multiplication of a neighbor, leading to neutral drift dynamics in which clones expand and contract at random until they either take over the crypt or they are lost. Combined with long-term clonal fate data, we show that the rate of stem cell replacement is comparable to the cell division rate, implying that neutral drift and symmetrical cell divisions are central to stem cell homeostasis.