Distinct Self-Renewal and Differentiation Phases in the Niche of Infrequently Dividing Hair Follicle Stem Cells

Abstract

Summary In homeostasis of adult vertebrate tissues, stem cells are thought to self-renew by infrequent and asymmetric divisions that generate another stem cell daughter and a progenitor daughter cell committed to differentiate. This model is based largely on in vivo invertebrate or in vitro mammal studies. Here we examine the dynamic behaviour of adult hair follicle stem cells in their normal setting by employing mice with repressible H2B-GFP expression to track cell divisions and Cre inducible mice to perform long-term single cell lineage tracing. We provide direct evidence for the infrequent stem cell division model in intact tissue. Moreover, we find that differentiation of progenitor cells occurs at different times and tissue locations than self-renewal of stem cells. Distinct fates of differentiation or self-renewal are assigned to individual cells in a temporal-spatial manner. We propose that large clusters of tissue stem cells behave as populations, whose maintenance involves unidirectional daughtercell fate decisions.

Hair follicle and interfollicular epidermal stem cells make varying contributions to wound regeneration

“…22 To assess the contribution of IFE-derived keratinocytes, we performed lineage tracing studies using mice expressing an inducible Keratin 14 (K14) promoter-driven Cre ERT allele coupled with the YFP reporter (K14;YFP mice). 21 We and others have previously shown that upon tamoxifen treatment, these mice display recombination primarily in the IFE 23,24 (Fig. 1A).…”

The circadian molecular clock creates epidermal stem cell heterogeneity

“…1d and Supplementary Table 1). Intriguingly, although the bulge is inactive at P18-19, both populations differed in the expression of a significant number of genes previously shown to constitute the bulge signature 2,3,12,24 . Venus bright bulge stem cells expressed higher levels (between 1.4-to 3-fold) of Wnt-signalling factors, including Tcf3, Fzd2/3, Sox9, Lhx2, Lgr5, Lef1, Dkk3 and Dab2, as well as TGF-b-inhibitory factors such as Smad7, Ltbp2-4, Smurf, Lefty and Cul1 (Fig.…”

“…Robust TGF-b and Bmp signals act as 'activation breaks', rendering bulge cells dormant during the resting phase of the hair cycle (telogen) [9][10][11] . At the onset of the growth phase (anagen), bulge cells respond to Wnt signals by migrating into the lower proliferative hair germ region, where they contribute to follicle growth [12][13][14][15] . Subsequently, at mid-anagen, the bulge undergoes a second round of activation, which replenishes cells lost at the onset of anagen 2,3 .…”

“…Subsequently, at mid-anagen, the bulge undergoes a second round of activation, which replenishes cells lost at the onset of anagen 2,3 . However, the response of bulge stem cells to activating stimuli is a heterogeneous process, as only a subset of them become active during either stage of activation 12,13 . The nature of such niche heterogeneity is currently unknown.…”

Biology of Human Hair: Know Your Hair to Control It

“…On the other hand, forced activation of b-catenin signaling promotes HF fate in both embryonic and postnatal skin [67,[73][74][75]. Recent studies also suggest that another pathway, the ectodysplasin signaling pathway, is critical for the induction and maintenance of placode [76,77].…”