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

SummaryIn 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 behavior 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 daughter-cell-fate decisions

Runx1 modulates adult hair follicle stem cell emergence and maintenance from distinct embryonic skin compartments

Runx1 controls timing of adult HSFC and short-term progenitor emergence in the embryonic epithelium and HFSC differentiation and long-term skin integrity in embryonic mesenchyme

Targeting a Transcriptional Activator Induces Changes in Large-Scale Chromatin Structure and Nuclear Positioning

80 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2000.This study addresses the relationship between transcriptional activation and large-scale chromatin structure and nuclear positioning. We have used an artificial system to target large amounts of the very strong viral transcriptional activator, VP16, to specific chromosome sites. The rationale of this approach is to use this exaggerated system to amplify effects on large-scale chromatin to the extent where they could be easily analyzed. We have demonstrated a re-programming of the cell-cycle dependent sequence of intranuclear positioning of a chromosome site, by the targeting of VP16 transcriptional activator. For a different chromosome site we describe a striking remodeling of chromatin structure including unfolding of a 90 Mbp heterochromatic chromosome arm into an extended 25--40 mum chromonema fiber, remodeling of this fiber in a novel subnuclear domain, and propagation of unfolding over hundreds of kilobase pairs. These changes occurred even in the absence of transcription and were accompanied by an increase in transcriptional activation, localized histone hyperacetylation, and recruitment of three histone acetyltransferases. Based on the observed propagation of changes in large-scale chromatin structure, we suggest a possible rationale for the observed clustering of housekeeping genes within Mbp-sized chromosome sites.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD

Alk1 acts in non-endothelial VE-cadherin+ perineurial cells to maintain nerve branching during hair homeostasis

Abstract Vascular endothelial (VE)-cadherin is a well-recognized endothelial cell marker. One of its interacting partners, the TGF-β receptor Alk1, is essential in endothelial cells for adult skin vasculature remodeling during hair homeostasis. Using single-cell transcriptomics, lineage tracing and gene targeting in mice, we characterize the cellular and molecular dynamics of skin VE-cadherin+ cells during hair homeostasis. We describe dynamic changes of VE-cadherin+ endothelial cells specific to blood and lymphatic vessels and uncover an atypical VE-cadherin+ cell population. The latter is not a predicted adult endovascular progenitor, but rather a non-endothelial mesenchymal perineurial cell type, which forms nerve encapsulating tubular structures that undergo remodeling during hair homeostasis. Alk1 acts in the VE-cadherin+ perineurial cells to maintain proper homeostatic nerve branching by enforcing basement membrane and extracellular matrix molecular signatures. Our work implicates the VE-cadherin/Alk1 duo, classically known as endothelial-vascular specific, in perineurial-nerve homeostasis. This has broad implications in vascular and nerve disease

Defining the epithelial stem cell niche in skin.

Many adult regenerative cells divide infrequently but have high proliferative capacity. We developed a strategy to fluorescently label slow-cycling cells in a cell type-specific fashion. We used this method to purify the label-retaining cells (LRCs) that mark the skin stem cell (SC) niche. We found that these cells rarely divide within their niche but change properties abruptly when stimulated to exit. We determined their transcriptional profile, which, when compared to progeny and other SCs, defines the niche. Many of the >100 messenger RNAs preferentially expressed in the niche encode surface receptors and secreted proteins, enabling LRCs to signal and respond to their environment.Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.info:eu-repo/semantics/publishe