Stem cell dynamics in mouse hair follicles A story from cell division counting and single cell lineage tracing

Understanding tissue stem cell behavior is a prerequisite for elucidating the mechanisms that govern their self-renewal and differentiation. Previously, we provided single cell lineage tracing and proliferation history data (based on H2B-GFP label dilution over time) in mouse hair follicles. We proposed a population deterministic model with symmetric stem cell fate decisions throughout life. Here we provide data suggesting that in hair follicle stem cells the self-renewing divisions within the niche (bulge) are symmetric with respect to localization of daughter cells near the basement membrane, an important niche component. In contrast, when cells migrate from the niche to the differentiating zone where they become short-lived progenitors, their daughter cells can adopt assymetric orientation relative to the basement membrane. Furthermore, we document the dynamic re-localization of cells within the bulge to accommodate the hair follicle morphological changes through the hair cycle. In addition, we provide a method to compute the change in number of cells generated by division from H2B-GFP pulse-chase data, and to estimate the minimum cell loss encountered when the fold change can be experimentally determined. We computed a minimum of 42% of bulge cell loss during one hair cycle, a massive rate of loss previously unrecognized. Finally, we showed that a multipotent population of cells found at the junction zone between hair follicle and epidermis, known to express Lrig1, cycle more rapidly than some other hair follicle compartments.