Hair follicle stem cell progeny heal blisters while pausing skin development.

Injury in adult tissue generally reactivates developmental programs to foster regeneration, but it is not known whether this paradigm applies to growing tissue. Here, by employing blisters, we show that epidermal wounds heal at the expense of skin development. The regenerated epidermis suppresses the expression of tissue morphogenesis genes accompanied by delayed hair follicle (HF) growth. Lineage tracing experiments, cell proliferation dynamics, and mathematical modeling reveal that the progeny of HF junctional zone stem cells, which undergo a morphological transformation, repair the blisters while not promoting HF development. In contrast, the contribution of interfollicular stem cell progeny to blister healing is small. These findings demonstrate that HF development can be sacrificed for the sake of epidermal wound regeneration. Our study elucidates the key cellular mechanism of wound healing in skin blistering diseases.

Substrate membrane bearing close-packed array of micron-level pillars incrassates air-exposed three-dimensional epidermal equivalent model.

BACKGROUND: We showed previously that a thick three-dimensional epidermal equivalent can be constructed with passaged keratinocytes on a patterned surface. MATERIAL AND METHODS: We first carried out computer simulations of a three-dimensional epidermal equivalent model built on close-packed arrays of 10 µm, 15 µm, 20 µm, 30 µm, and 60 µm diameter pillars. Based on these predictions, we evaluated epidermal equivalents built on a series of porous plastic membranes bearing arrays of pillars 15 µm, 20 µm, 25 µm, 30 µm, and 50 µm in diameter. RESULTS: The simulations predicted that a model having near-physiological thickness would be formed on 15 ~ 30 µm pillars. In the results of in vitro study, the thickest epidermal equivalent was obtained on the 20 µm pillars. Epidermal differentiation markers, filaggrin and loricrin, were expressed at the upper layer of the epidermal equivalent model, and tight-junction proteins, claudin-1 and ZO-1, were expressed on the cell membranes. BrdU-positive cells were observed at the base and also at the top of the pillars. CONCLUSION: The results of the study suggested that mathematical modeling might be a useful tool to guide biological studies.

Temporal coherency of mechanical stimuli modulates tactile form perception.

The human hand can detect both form and texture information of a contact surface. The detection of skin displacement (sustained stimulus) and changes in skin displacement (transient stimulus) are thought to be mediated in different tactile channels; however, tactile form perception may use both types of information. Here, we studied whether both the temporal frequency and the temporal coherency information of tactile stimuli encoded in sensory neurons could be used to recognize the form of contact surfaces. We used the fishbone tactile illusion (FTI), a known tactile phenomenon, as a probe for tactile form perception in humans. This illusion typically occurs with a surface geometry that has a smooth bar and coarse textures in its adjacent areas. When stroking the central bar back and forth with a fingertip, a human observer perceives a hollow surface geometry even though the bar is physically flat. We used a passive high-density pin matrix to extract only the vertical information of the contact surface, suppressing tangential displacement from surface rubbing. Participants in the psychological experiment reported indented surface geometry by tracing over the FTI textures with pin matrices of the different spatial densities (1.0 and 2.0 mm pin intervals). Human participants reported that the relative magnitude of perceived surface indentation steeply decreased when pins in the adjacent areas vibrated in synchrony. To address possible mechanisms for tactile form perception in the FTI, we developed a computational model of sensory neurons to estimate temporal patterns of action potentials from tactile receptive fields. Our computational data suggest that (1) the temporal asynchrony of sensory neuron responses is correlated with the relative magnitude of perceived surface indentation and (2) the spatiotemporal change of displacements in tactile stimuli are correlated with the asynchrony of simulated sensory neuron responses for the fishbone surface patterns. Based on these results, we propose that both the frequency and the asynchrony of temporal activity in sensory neurons could produce tactile form perception.

A computational model of the epidermis with the deformable dermis and its application to skin diseases.

The skin barrier is provided by the organized multi-layer structure of epidermal cells, which is dynamically maintained by a continuous supply of cells from the basal layer. The epidermal homeostasis can be disrupted by various skin diseases, which often cause morphological changes not only in the epidermis but in the dermis. We present a three-dimensional agent-based computational model of the epidermis that takes into account the deformability of the dermis. Our model can produce a stable epidermal structure with well-organized layers. We show that its stability depends on the cell supply rate from the basal layer. Modeling the morphological change of the dermis also enables us to investigate how the stiffness of the dermis affects the structure and barrier functions of the epidermis. Besides, we show that our model can simulate the formation of a corn (clavus) by assuming hyperproliferation and rapid differentiation. We also provide experimental data for human corn, which supports the model assumptions and the simulation result.

Competition between global feedback and diffusion in coupled Belousov-Zhabotinsky oscillators.

The Belousov-Zhabotinsky (BZ) reaction is a famous experimental model for chemical oscillatory reaction and pattern formation. We herein study a diffusive coupled system of two oscillators with global feedback using the photosensitive BZ reaction both experimentally and theoretically. The coupled oscillator showed in-phase and antiphase oscillations depending on the strength of diffusive coupling and light feedback. Moreover, we analyzed our model to locate the bifurcational origin and found the reconnection of the bifurcation branches for antiphase oscillation, which was induced by the competition between global feedback and the diffusion effect.