Uniquely among mammalian organs, skin is capable of marked size change in adults, yet the mechanisms underlying this notable capacity are unclear. Here, we use a system of controlled tissue expansion in mice to uncover cellular and molecular determinants of skin growth. Through machine learning–guided three-dimensional tissue reconstruction, we capture morphometric changes in growing skin. We find that most growth is driven by the proliferation of the epidermis in response to mechanical tension, with more limited changes in dermal and subdermal compartments. Epidermal growth is achieved through preferential activation and differentiation of Lgr6 + stem cells of the epidermis, driven in part by the Hippo pathway. By single-cell RNA sequencing, we uncover further changes in mechanosensitive and metabolic pathways underlying growth control in the skin. These studies point to therapeutic strategies to enhance skin growth and establish a platform for understanding organ size dynamics in adult mammals.

Fibrosis is a major health burden across diseases and organs. To remedy this, we study wound‐induced hair follicle neogenesis (WIHN) as a model of non‐fibrotic healing that recapitulates embryogenesis for de novo hair follicle morphogenesis after wounding. We previously demonstrated that TLR3 promotes WIHN through binding wound‐associated dsRNA, the source of which is still unclear. Here, we find that multiple distinct contexts of high WIHN all show a strong neutrophil signature. Given the correlation between neutrophil infiltration and endogenous dsRNA release, we hypothesized that neutrophil extracellular traps (NETs) likely release nuclear spliceosomal U1 dsRNA and modulate WIHN. However, rather than enhance regeneration, we find mature neutrophils inhibit WIHN such that mice with mature neutrophil depletion exhibit higher WIHN. Similarly, Pad4 null mice, which are defective in NET production, show augmented WIHN. Finally, using single‐cell RNA sequencing, we identify a dramatic increase in mature and activated neutrophils in the wound beds of low regenerating Tlr3−/− mice. Taken together, these results demonstrate that although mature neutrophils are stimulated by a common pro‐regenerative cue, their presence and NETs hinder regeneration.

This paper presents a distributed multi-class Gaussian process (MCGP) algorithm for ground vehicle classification using acoustic data. In this algorithm, the harmonic structure analysis is used to extract features for GP classifier training. The predictions from local classifiers are then aggregated into a high-level prediction to achieve the decision-level fusion, following the idea of divide-and-conquer. Simulations based on the acousticseismic classification identification data set (ACIDS) confirm that the proposed algorithm provides competitive performance in terms of classification error and negative log-likelihood (NLL), as compared to an MCGP based on the data-level fusion where only one global MCGP is trained using data from all the sensors.

After injury, a timely inflammatory response that involves the recruitment of blood-derived circulating monocytes is essential for tissue repair. Once in the wound bed, these cells differentiate into macrophages during the inflammatory phase, a process that goes awry during aging in chronic non-healing wounds. Cell differentiation is a highly energydemanding process, and metabolic substrates present in the wound bed niche are important for the wound healing outcome. We previously demonstrated that dermal adipocytes release fatty acids into wound beds after injury to promote inflammation, yet the function of adipocyte-derived fatty acids in the initiation of the inflammatory response after injury is not known. To unveil the role of adipocytes as providers of fatty acids used to fuel the metabolic requirements of immune cell differentiation, we set out to evaluate their role on monocyte to macrophage differentiation in the skin wound bed. Here, we utilize in vivo mouse models of skin injury and metabolic assays to reveal that monocytes utilize fatty acids to fuel metabolic programs that induce macrophage differentiation. We show that extracellular vesicles (EVs) loaded with lipids are actively taken up by monocytes in vitro and in mice in vivo. Using realtime respirometry, we show that these fatty acids activate the b-oxidation metabolic pathway in monocytes and its inhibition leads to the abrogation of macrophage differentiation. Furthermore, we show that with age, not only adipocyte-derived EV production was impaired, but more importantly, these particles were less effective in rewiring monocyte metabolism towards oxidative phosphorylation. In summary, our findings reveal an essential adipocyte-monocyte metabolic axis that controls inflammation in the wound bed niche.