Project description:We performed transcriptome analysis and multimodal data integration of the transcriptome and the microbiome of the skin of Mycosis fungoides Patients.
Project description:Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system, which currently lacks effective therapies that provide regeneration and stop disease progression. A suggested link is anticipated between the development of progressive MS (PMS) and aging, as suggested by recent work identifying hallmarks of cellular senescence in numerous cell types both in vitro with patient cell lines and in vivo in the post-mortem MS brain, including neural stem cells (NSCs). Using an inducible system, directly reprogramming human fibroblasts into induced NSCs (iNSCs), we generated control and PMS iNSC cell lines, which was found to maintain epigenetic age. Here we performed multi-omics, including bulk RNA, single-cell (sc) RNA, single-nucleus (sn) RNA and ATAC, and whole genome bisulfite sequencing. Here, we show that PMS iNSCs have overall increases in senescence and inflammatory associated genes using bulk sequencing. We next identified a unique subcluster of cells within the PMS iNSCs that have a pro-inflammatory and senescent phenotype, associated with interferon gene activation using sc-RNA seq. Within this specific subcluster there is higher expression of genes associated with inflammatory protein secretion, as well as the senescence associated secretory phenotype (SASP). A similar clustering pattern was observed in the ATAC-seq data, a large main cluster and a small inflammatory cluster primarily comprising of PMS iNSCs. Differentially accessible regions within the PMS cluster revealed promoter sites of inflammatory-associated genes to be more accessible correlating with gene expression. Our results highlight a novel cellular mechanism in PMS wherein NSCs are interferon-responsive and senescent-like which may impact other cells within the lesion leading to chronic inflammation.
Project description:In this study, we conducted an integrated analysis of skin measurements, clinical BSTI surveys, and the skin microbiome of 950 Korean subjects to examine the ideal skin microbiome-biophysical association. By utilizing four skin biophysical parameters, we identified four distinct Korean Skin Cutotypes (KSCs) and categorized the subjects into three aging groups based on their age distribution. We established strong connections between 15 core genera and the four KSC types within the three aging groups, revealing three prominent clusters of the facial skin microbiome. Together with skin microbiome variations, skin tone/elasticity distinguishes aging groups while oiliness/hydration distinguishes individual differences within aging groups. Our study provides prospective reality data for customized skin care based on the microbiome environment of each skin type.
Project description:The skin Microbiome stratifies Patients with CTCL into two subgroups. One subgroup has a balanced microbiome, while the other subgroups has a skin dybiosis with S. aureus outgrowth. This is accompanied by impaired TCR repertoire and poor clinical outcome.
Project description:The skin Microbiome stratifies Patients with CTCL into two subgroups. One subgroup has a balanced microbiome, while the other subgroups has a skin dybiosis with S. aureus outgrow. This is accompanied by impaired TCR repertoir and poor clinical outcome.
Project description:Characteization host-microbiome interactions in patients with allergic (model: atopic dermatitis) and autoimmune (model: psoriasis) diseases by integration of microarray transcriptome data with 16S microbial profiling. 6mm punch biopsies were collected from the skin of atopic dermatitis and psoriasis patients alongside healthy volunteers, and subjected to analysis using Affymetrix Human Gene ST 2.1 arrays.
Project description:Skin bacteria impact melanoma related pathways Melanoma represents the most lethal form of skin cancer, with rising numbers of annual incidences worldwide. In an effort to identify new risk factors that promote melanoma development, the contribution of the skin microbiome gained increasing attention. Previous studies already demonstrated an altered composition of the skin microbiome on melanoma sites. Yet, the underlying mechanisms of the interplay between the microbiome and melanoma progression remain elusive. We established a novel co-culture system capable to study host microbiome interactions during melanoma progression in situ. This system consists of a commercial 3D melanoma skin model colonized with skin bacteria obtained from a skin swab of a healthy volunteer. The models showed a stable co-colonization over a period of 12 days, with Streptococcus being the most abundant genus on the last day of cultivation. Transcriptome profiles revealed significant differences in colonized models compared to control. In particular, pathways involved in melanoma progression, like RAF/MAP and PI3K kinase, were upregulated in colonized models. This correlates with the augmented release of the cytokines VEGF, PIGF, and GM-CSF as well as the typical melanoma markers MIA and S100B. Furthermore, the data were supported by an active epithelial-mesenchymal transition in colonized skin models. Taken together, the bacterial community seems to promote the progression of melanoma in our established system, hence we provide an elegant method to elucidate the microbiome’s impact on cancer development in situ.