Adult hair follicle stem cells do not retain the older DNA strands in vivo during normal tissue homeostasis

Tissue stem cells have been proposed to segregate the chromosomes asymmetrically (in a non-random manner), thereby retaining preferentially the older “immortal” DNA strands bearing the stemness characteristics into one daughter cell, whereas the newly synthesized strands are segregated to the other daughter cell that will commit to differentiation. Moreover, this non-random segregation would protect the stem cell genome from accumulating multiple mutations during repeated DNA replication. This long-standing hypothesis remains an active subject of study due to conflicting results for some systems and lack of consistency among different tissue stem cell populations. In this review, we will focus on work done in the hair follicle, which is one of the best-understood vertebrate tissue stem cell system to date. In cell culture analysis of paired cultured keratinocytes derived from hair follicle, stem cells suggested a non-random segregation of chromosome with respect to the older DNA strand. In vivo, the hair follicle stem cells appear to self-renew and differentiate at different phases of their homeostatic cycle. The fate decisions occur in quiescence when some stem cells migrate out of their niche and commit to differentiation without self-renewal. The stem cells left behind in the niche self-renew symmetrically and randomly segregate the chromosomes at each division, making more stem cells. This model seems to apply to at least a few other vertebrate tissue stem cells in vivo.     

Aberrations induced in wavefront-guided laser refractive surgery due to shifts between natural and dilated pupil center locations

PURPOSE: To determine the aberrations induced in wavefront-guided laser refractive surgery due to shifts in pupil center location from when aberrations are measured preoperatively (over a dilated pupil) to when they are corrected surgically (over a natural pupil). SETTING: Center for Visual Science and Department of Ophthalmology, University of Rochester, Rochester, New York, USA. METHODS: Shifts in pupil center were measured between dilated phenylephrine hydrochloride (Neo-Synephrine [2.5%]) and nonpharmacological mesopic conditions in 65 myopic eyes treated with wavefront-guided laser in situ keratomileusis (Technolas 217z, Bausch & Lomb). Each patient's preoperative and 6-month postoperative wave aberrations were measured over the dilated pupil. Aberrations theoretically induced by decentration of a wavefront-guided ablation were calculated and compared with those measured 6 months postoperatively (6.0 mm pupil). RESULTS: The mean magnitude of pupil center shift was 0.29 mm +/- 0.141 (SD) and usually occurred in the inferonasal direction as the pupil dilated. Depending on the magnitude of shift, the fraction of the higher-order postoperative root-mean-square wavefront error that could be due theoretically to pupil center decentrations was highly variable (mean 0.26 +/- 0.20 mm). There was little correlation between the calculated and 6-month postoperative wavefronts, most likely because pupil center decentrations are only 1 of several potential sources of postoperative aberrations. CONCLUSIONS: Measuring aberrations over a Neo-Synephrine-dilated pupil and treating them over an undilated pupil typically resulted in a shift of the wavefront-guided ablation in the superotemporal direction and an induction of higher-order aberrations. Methods referencing the aberration measurement and treatment with respect to a fixed feature on the eye will reduce the potential for inducing aberrations due to shifts in pupil center.