The immortal DNA strand hypothesis, proposed in 1975 by John Cairns as a mechanism for adult stem cells to minimize mutations in their genomes.
Passing on these replication errors would allow adult stem cells to reduce their rate of accumulation of mutations that could lead to serious genetic disorders such as cancer.
Experimentally, adult stem cells are undergoing symmetric divisions during growth and after wound healing, and are not yet determined at neonatal stages.
In the label-release assay, the goal is to mark the newly synthesized DNA that is normally passed on to the daughter (non-stem) cell.
One of the earliest studies by Karl Lark et al. demonstrated co-segregation of DNA in the cells of plant root tips.
[4] Later studies by Christopher Potten et al. (2002),[2] using pulse/chase experiments with tritiated thymidine, found long-term label-retaining cells in the small intestinal crypts of neonatal mice.
Joshua Merok et al. from the lab of James Sherley engineered mammalian cells with an inducible p53 gene that controls asymmetric divisions.
These asymmetrically dividing cells provide an in vitro model for demonstration and investigation of immortal strand mechanisms.
Scientists have strived to demonstrate that this immortal DNA strand mechanism exists in vivo in other types of adult stem cells.
[3] Soon after, scientists from the laboratory of Derek van der Kooy showed that mice have neural stem cells that are BrdU-retaining and continue to be mitotically active.
[11] During larval development there was rapid depletion of older DNA template strands from stem cell niches in the retina, brain and intestine.
[11] Using high resolution microscopy, no evidence of asymmetric template strand segregation (in over 100 cell pairs) was found, making it improbable that in developing zebrafish asymmetric DNA segregation avoids mutational burden as proposed by the immortal strand hypothesis.
[12] Emmanuel David Tannenbaum and James Sherley developed a quantitative model describing how repair of point mutations might differ in adult stem cells.