Hair follicles: Secret to prevent scars?: Although some animals easily regenerate limbs and heal broken flesh, mammals are generally not so gifted. Wounding can leave scars, which are characterized by a lack of hair follicles and cutaneous fat. Plikus et al. now show that hair follicles in both mice and humans can convert myofibroblasts, the predominant dermal cell in a wound, into adipocytes (see the Perspective by Chan and Longaker). The hair follicles activated the bone morphogenetic protein (BMP) signaling pathway and adipocyte transcription factors in the myofibroblast. Thus, it may be possible to reduce scar formation after wounding by adding BMP. Science , this issue p. 748 ; see also p. 693
From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues Network, which aims to create a reference catalogue of somatic mutations and their clonal patterns across 19 different tissue sites from 150 non-diseased donors and develop new technologies and computational tools to detect somatic mutations and assess their phenotypic consequences, including clonal expansions. This strategy enables a comprehensive examination of the mutational landscape across the human body, and provides a comparison baseline for somatic mutation in diseases. This will lead to a deep understanding of somatic mutations and clonal expansions across the lifespan, as well as their roles in health, in ageing and, by comparison, in diseases.
The control principles behind robust cyclic regeneration of hair follicles (HFs) remain unclear. Using multi-scale modeling, we show that coupling inhibitors and activators with physical growth of HFs is sufficient to drive periodicity and excitability of hair regeneration. Model simulations and experimental data reveal that mouse skin behaves as a heterogeneous regenerative field, composed of anatomical domains where HFs have distinct cycling dynamics. Interactions between fast-cycling chin and ventral HFs and slow-cycling dorsal HFs produce bilaterally symmetric patterns. Ear skin behaves as a hyper-refractory domain with HFs in extended rest phase. Such hyper-refractivity relates to high levels of BMP ligands and WNT antagonists, in part expressed by ear-specific cartilage and muscle. Hair growth stops at the boundaries with hyper-refractory ears and anatomically discontinuous eyelids, generating wave-breaking effects. We posit that similar mechanisms for coupled regeneration with dominant activator, hyper-refractory, and wave-breaker regions can operate in other actively renewing organs.
21 August 2023 in Journal of Investigative Dermatology
Objective: The objective of this study is to provide a comparative analysis of variant clusters and their relevance across Africa, America, Europe, and Asia, in order to understand the evolutionary patterns of the virus across different regions and to inform the development of targeted interventions and genomic surveillance eforts. Methods: The study analyzed the global lineage evolution pattern of 74, 075 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from 32 countries across four continents, focusing on variant clusters and their relevance across regions. Variants were weighted according to their hierarchical level. The correlation between variants was visualized through Dimensionality reduction analysis and Pairwise Pearson's correlation. We presented a reconstructed phylogenetic tree based on correlation analysis and variant weights. Results: The analysis revealed that each continent had distinct variant clusters and different evolutionary patterns. The Americas had two clustered variants before lineage divergence and a downstream confluence lineage, Europe had bifurcation into two global lineages with an early occurrence of certain cluster while Asia had a downstream confluence of two large lineages diverging by two distinct clusters. Based on the cluster patterns of shared variants of the SARS-CoV-2 virus, Africa demonstrated a relatively clear distinction among three distinct regions. Conclusions: The study provides insights into the evolutionary patterns of SARS-CoV-2 and highlights the importance of international collaboration in tracking and responding to emerging variants. The study found that the global pandemic was driven by Omicron variants that evolved with significant differences between countries and regions, and with different patterns across continents.