Periodontitis affects billions of people worldwide. To address relationships of periodontal niche cell types and microbes in periodontitis, we generated an integrated single-cell RNA sequencing (scRNAseq) atlas of human periodontium (34-sample, 105918-cell), including sulcular and junctional keratinocytes (SK/JKs). SK/JKs displayed altered differentiation states and were enriched for effector cytokines in periodontitis. Single-cell metagenomics revealed 37 bacterial species with cell-specific tropism. Fluorescence in situ hybridization detected intracellular 16 S and mRNA signals of multiple species and correlated with SK/JK proinflammatory phenotypes in situ. Cell-cell communication analysis predicted keratinocyte-specific innate and adaptive immune interactions. Highly multiplexed immunofluorescence (33-antibody) revealed peri-epithelial immune foci, with innate cells often spatially constrained around JKs. Spatial phenotyping revealed immunosuppressed JK-microniches and SK-localized tertiary lymphoid structures in periodontitis. Here, we demonstrate impacts on and predicted interactomics of SK and JK cells in health and periodontitis, which requires further investigation to support precision periodontal interventions in states of chronic inflammation.

B-lymphocyte-induced maturation protein 1 (Blimp1) is a transcriptional repressor that regulates cell growth and differentiation in multiple tissues, including skin. Although in the epidermis Blimp1 is important for keratinocyte and sebocyte differentiation, its role in dermal fibroblasts is unclear. Here we show that Blimp1 is dynamically regulated in dermal papilla cells during hair follicle (HF) morphogenesis and the postnatal hair cycle, preceding dermal Wnt/β-catenin activation. Blimp1 ablation in E12.5 mouse dermal fibroblasts delayed HF morphogenesis and growth and prevented new HF formation after wounding. By combining targeted quantitative PCR screens with bioinformatic analysis and experimental validation we demonstrated that Blimp1 is both a target and a mediator of key dermal papilla inductive signaling pathways including transforming growth factor-β and Wnt/β-catenin. Epidermal overexpression of stabilized β-catenin was able to override the HF defects in Blimp1 mutant mice, underlining the close reciprocal relationship between the dermal papilla and adjacent HF epithelial cells. Overall, our study reveals the functional role of Blimp1 in promoting the dermal papilla inductive signaling cascade that initiates HF growth.

Epithelial tissues are the most rapidly dividing tissues in the body, holding a natural ability for renewal and regeneration. This ability is crucial for survival as epithelia are essential to provide the ultimate barrier against the external environment, protecting the underlying tissues. Tissue stem and progenitor cells are responsible for self-renewal and repair during homeostasis and following injury. Upon wounding, epithelial tissues undergo different phases of haemostasis, inflammation, proliferation and remodelling, often resulting in fibrosis and scarring. In this review, we explore the phenotypic differences between the skin, the oesophagus and the oral mucosa. We discuss the plasticity of these epithelial stem cells and contribution of different fibroblast subpopulations for tissue regeneration and wound healing. While these epithelial tissues share global mechanisms of stem cell behaviour for tissue renewal and regeneration, the oral mucosa is known for its outstanding healing potential with minimal scarring. We aim to provide an updated review of recent studies that combined cell therapy with bioengineering exporting the unique scarless properties of the oral mucosa to improve skin and oesophageal wound healing and to reduce fibrotic tissue formation. These advances open new avenues toward the ultimate goal of achieving scarless wound healing.