Direct measurements of human colon crypt stem cell niche genetic fidelity: the role of chance in non-darwinian mutation selection

Frontiers in Oncology
Haeyoun Kang, Darryl Shibata

Abstract

Perfect human stem cell genetic fidelity would prevent aging and cancer. However, perfection would be difficult to achieve, and aging is universal and cancers common. A hypothesis is that because mutations are inevitable over a human lifetime, downstream mechanisms have evolved to manage the deleterious effects of beneficial and lethal mutations. In the colon, a crypt stem cell architecture reduces the number of mitotic cells at risk for mutation accumulation, and multiple niche stem cells ensure that a lethal mutation within any single stem cell does not lead to crypt death. In addition, the architecture of the colon crypt stem cell niche may harness probability or chance to randomly discard many beneficial mutations that might lead to cancer. An analysis of somatic chromosome copy number alterations (CNAs) reveals a lack of perfect fidelity in individual normal human crypts, with age-related increases and higher frequencies in ulcerative colitis, a proliferative, inflammatory disease. The age-related increase in somatic CNAs appears consistent with relatively normal replication error and cell division rates. Surprisingly, and similar to point mutations in cancer genomes, the types of crypt mutations were more consistent with ...Continue Reading

References

Mar 13, 2016·Seminars in Oncology·Asad UmarErnest T Hawk
Dec 15, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Mei Guo, Jun Dou
Jun 10, 2015·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Aleah F CaulinCarlo C Maley
Mar 27, 2019·Molecular Biology and Evolution·Bingjie ChenChung-I Wu
Jan 31, 2018·Physical Biology·A J FendrikE Rotondo
Nov 3, 2018·Frontiers in Immunology·Ibrahim Al BakirTrevor A Graham
Jan 29, 2019·Frontiers in Oncology·Thomas BuderAnja Voss-Böhme
Dec 20, 2019·Nature·Nobuyuki KakiuchiSeishi Ogawa

Related Concepts

Genome
Cell Division
Inflammatory Disorder
Sample Fixation
Stem Cell Niche
Chromosomes
Myositis
Alopecia, Epilepsy, Pyorrhea, Mental Subnormality
Diploid Cell
Crypt of Lieberkuhn

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