Multiscale spatial mapping of cell populations across anatomical sites in healthy human skin and basal cell carcinoma

\ua9 2024 National Academy of Sciences. All rights reserved.Our understanding of how human skin cells differ according to anatomical site and tumour formation is limited. To address this, we have created a multiscale spatial atlas of healthy skin and basal cell carcinoma (BCC), incorporating in vivo optical coherence tomography, single-cell RNA sequencing, spatial global transcriptional profiling, and in situ sequencing. Computational spatial deconvolution and projection revealed the localisation of distinct cell populations to specific tissue contexts. Although cell populations were conserved between healthy anatomical sites and in BCC, mesenchymal cell populations including fibroblasts and pericytes retained signatures of developmental origin. Spatial profiling and in silico lineage tracing support a hair follicle origin for BCC and demonstrate that cancer-associated fibroblasts are an expansion of a POSTN+ subpopulation associated with hair follicles in healthy skin. RGS5+ pericytes are also expanded in BCC suggesting a role in vascular remodelling. We propose that the identity of mesenchymal cell populations is regulated by signals emanating from adjacent structures and that these signals are repurposed to promote the expansion of skin cancer stroma. The resource we have created is publicly available in an interactive format for the research community

Complete genome sequences of African Salmonella enterica serovar enteritidis clinical isolates associated with bloodstream infection

We report the complete genome sequencing and annotation of four Salmonella enterica serovar Enteritidis isolates, two that are representative of the Central/Eastern African clade (CP255 and D7795) and two of the Global Epidemic clade (A1636 and P125109)

Peptide Folding in Cellular Environments: A Monte Carlo and Markov Modeling Approach

Steric interactions with surrounding macromolecules tend to favor the compact native state of a globular protein over its unfolded state. However, in experiments conducted in cells and concentrated protein solutions, both stabilization and destabilization of proteins have been observed, compared to dilute-solution conditions. Therefore, in order to understand the effects of surrounding macromolecules on protein properties such as stability, there is a need for computational modeling beyond the level of hard-sphere crowders. Here, we discuss some recent exploratory studies of peptide folding in the presence of explicit protein crowders, carried out by us using an all-atom Monte Carlo-based approach along with an implicit solvent force field. For interpreting the simulation data, time-lagged independent component analysis and Markov state modeling are used