Human hair genealogies and stem cell latency

Jung Yeon Kim,Darryl Shibata,Simon Tavaré

doi:10.1186/1741-7007-4-2

Abstract

BackgroundStem cells divide to reproduce themselves and produce differentiated progeny. A fundamental problem in human biology has been the inability to measure how often stem cells divide. Although it is impossible to observe every division directly, one method for counting divisions is to count replication errors; the greater the number of divisions, the greater the numbers of errors. Stem cells with more divisions should produce progeny with more replication errors.MethodsTo test this approach, epigenetic errors (methylation) in CpG-rich molecular clocks were measured from human hairs. Hairs exhibit growth and replacement cycles and "new" hairs physically reappear even on "old" heads. Errors may accumulate in long-lived stem cells, or in their differentiated progeny that are eventually shed.ResultsAverage hair errors increased until two years of age, and then were constant despite decades of replacement, consistent with new hairs arising from infrequently dividing bulge stem cells. Errors were significantly more frequent in longer hairs, consistent with long-lived but eventually shed mitotic follicle cells.ConclusionConstant average hair methylation regardless of age contrasts with the age-related methylation observed in human intestine, suggesting that error accumulation and therefore stem cell latency differs among tissues. Epigenetic molecular clocks imply similar mitotic ages for hairs on young and old human heads, consistent with a restart with each new hair, and with genealogies surreptitiously written within somatic cell genomes.

Highlights

Stem cells divide to reproduce themselves and produce differentiated progeny
The lack of age-related increase in hair methylation is consistent with infrequently-dividing stem cells because the average numbers of divisions during neogenesis and anagen are likely to be similar for all hairs
The stochastic nature of replication errors may hinder the interpretation of molecular clocks, and many questions remain [25], such approaches provide information that is difficult to obtain by other more precise methods

Summary

Introduction

Stem cells divide to reproduce themselves and produce differentiated progeny. Stem cells with more divisions should produce progeny with more replication errors. Each cell has its own genealogy, which starts from the zygote and ends with the current phenotype. The genealogy of a differentiated epithelial cell can be divided into three distinct phases: neogenesis or development between the zygote and tissue formation, stem cell latency, and differentiation (Figure 1). The stem cell phase is chronologically the longest because developing and differentiated cells survive for relatively short periods. It is uncertain how often stem cells divide because they are rare, difficult to culture, and lack unique identifying markers

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