Biology subjects

Dalessandri, T.

Publications and source records attributed to Dalessandri, T..

4 recordsLinked to original sources

bioRxiv2022

Molecular and spatial design of early skin development

A wealth of specialized cell populations within the skin facilitates its hair producing, protective, sensory and thermoregulatory functions, but how the vast cell-type diversity and tissue architecture develops is largely unexplored. Here, with single-cell transcriptomics, spatial cell-type assignment and cell-lineage tracing we deconstruct early embryonic mouse skin during the key transitions from seemingly uniform developmental precursor states to a multilayered, multilineage epithelium and complex dermal identity. We reveal the spatiotemporal emergence of hair-follicle-inducing, muscle-supportive, and fascia-forming fibroblasts. We also uncover the formation of the panniculus carnosus muscle, sprouting blood vessels without pericyte coverage, and the earliest residence of mast and dendritic immune cells in skin. Finally, we reveal an unexpected epithelial heterogeneity within the early single-layered epidermis and a signaling-rich periderm layer. Overall, this cellular blueprint of early skin development establishes histological landmarks - essential for placing cells in their spatial tissue context - and highlights unprecedented dynamical interactions among skin cells.

developmental biology↗

bioRxiv2022

Rare Gli1+ perivascular fibroblasts promote skin wound repair

Growing evidence suggests that perivascular cells play important roles in tissue repair of various organs. In the skin, the contribution and importance of these cells for wound repair is not resolved. Here we demonstrate that a specific Gli1+ subpopulation residing in the perivascular niche serves as an important cellular source for wound healing fibroblast. First, we show that Gli1 expression marks small subsets of both pericytes and perivascular adventitial cells. Upon injury both cell types rapidly responded already within their original niche, however only the progeny of Gli1+ adventitial cells expanded and differentiated into wound-contracting myofibroblasts. Genetic ablation of these cells significantly impaired wound healing, which was associated with the reduction of aSMA+ myofibroblast-mediated wound contraction. After wound closure these cells reverted to an aSMA-negative fibroblast state, and intriguingly, they persisted in wounds over long term and adopted a non-fibrotic fibroblast signature. In sum, our data sheds new light on the functional diversity of perivascular-cell subtypes in the skin, and proposes a new mesenchymal cell source that promotes wound healing.

cell biology↗

bioRxiv2019

The molecular anatomy of mouse skin during hair growth and rest

Skin homeostasis is orchestrated by dozens of cell types that together direct stem cell renewal, lineage commitment and differentiation. However, a systematic molecular atlas of full-thickness skin is lacking. Here, we used single-cell RNA-sequencing and mRNA-FISH to determine gene-expression identity and spatial location of skin cells during hair growth and rest. We defined 55 cell populations and made striking discoveries about the outer root sheath (ORS) and inner hair follicle layers that together coordinate hair production. The ORS is composed of two distinct cell types, companion layer cells resemble ORS and not inner layer cells, and we identified an asymmetric inner-layer structure with ORS cell identity. Moreover, the inner layers branch from transcriptionally uncommitted progenitors, and each lineage differentiation passes through an intermediate state. Altogether, we generated a comprehensive atlas with molecular and spatial information on epithelial and stromal cells, including fibroblasts, vascular and immune cells, that will spur new discoveries in skin biology.\n\nHIGHLIGHTS- Comprehensive single-cell transcriptome atlas of full-thickness skin\n- Outer root sheath (ORS) is composed of two distinct cell types\n- Companion layer transcriptionally resembles ORS\n- Transcriptional reconstruction of the internal hair follicle (HF) lineages\n- Molecular identification of an asymmetric HF-bulb structure\n- Spatial map of fibroblast subtypes in the skin\n- Online tool. http://kasperlab.org/tools

cell biology↗

bioRxiv2019

Transcriptional bursts explain autosomal random monoallelic expression and affect allelic imbalance

Transcriptional bursts render substantial biological noise in cellular transcriptomes. Here, we investigated the theoretical extent of monoallelic expression resulting from transcriptional bursting and how it compared to the amounts of monoallelic expression of autosomal genes observed in single-cell RNA-sequencing (scRNA-seq) data. We found that transcriptional bursting can explain frequent observations of autosomal monoallelic gene expression in cells. Importantly, the burst frequency largely determined the fraction of cells with monoallelic expression, whereas both burst frequency and size contributed to allelic imbalance. Allelic observations deviate from the expected when analysed across heterogeneous groups of cells, suggesting that allelic modelling can provide an unbiased assessment of heterogeneity within cells. Finally, large numbers of cells are required for analyses of allelic imbalance to avoid confounding observations from transcriptional bursting. Altogether, our results shed light on the implications of transcriptional burst kinetics on allelic expression patterns and phenotypic variation between cells.

genomics↗