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A single-cell atlas of the microenvironment of implanted biomaterials and computational analysis of the transcriptional signalling networks [single-cell RNA-seq]

ABSTRACT: A single-cell atlas of the microenvironment of implanted biomaterials and computational analysis of the transcriptional signalling networks [single-cell RNA-seq]

PROVIDER: PRJNA734269 | ENA |

REPOSITORIES: ENA

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A single-cell atlas of the microenvironment of implanted biomaterials and computational analysis of the transcriptional signalling networks [single-cell RNA-seq]

Project description:The understanding of the foreign-body responses to implanted biomaterials would benefit from the reconstruction of intracellular and intercellular signalling networks in the microenvironment surrounding the implant. Here, by leveraging single-cell RNA-sequencing data from 42,156 cells harvested from the site of implantation of either polycaprolactone or an extracellular-matrix-derived scaffold in a mouse model of volumetric muscle loss, we report a computational analysis of intercellular-signalling networks reconstructed from data of transcription-factor activation. We found that intercellular signalling networks can be clustered into modules associated with specific cell subsets, and that biomaterial-specific responses can be characterized by interactions between signalling modules for immune, fibroblast and tissue-specific cells. In a Il17ra–/¬– knockout mouse model, we validated that predicted IL-17-linked transcriptional targets led to concomitant changes in gene expression. Moreover, we identified cell subsets that had not been implicated in the responses to implanted biomaterials. Single-cell atlases of the cellular responses to implanted biomaterials will facilitate the design of implantable biomaterials and the understanding of the ensuing cellular responses.

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A single-cell atlas of the microenvironment of implanted biomaterials and computational analysis of the transcriptional signalling networks [bulk RNA-seq]

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A single-cell atlas of the microenvironment of implanted biomaterials and computational analysis of the transcriptional signalling networks

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A single-cell atlas of the microenvironment of implanted biomaterials and computational analysis of the transcriptional signalling networks

Project description:This SuperSeries is composed of the SubSeries listed below.

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Biomaterials direct functional B cell response in a material specific manner

Project description:B cells are an adaptive immune target of biomaterials development in vaccine research but despite their role in wound healing have not been studied tissue engineering and regenerative medicine. We evaluated the B cell response to biomaterial scaffold materials implanted in a muscle wound; a biological extracellular matrix (ECM) and synthetic polyester polycaprolactone. In the local muscle tissue, small numbers of B cells are recruited in response to tissue injury and biomaterial implantation. ECM materials induced plasmablasts in lymph nodes and antigen presentation in the spleen while the synthetic PCL implants delayed B cell migration and induced an antigen presenting phenotype. In muMt- mice lacking B cells, the fibrotic response to the synthetic biomaterials decreased. Immunofluorescence confirmed antigen presenting B cells in fibrotic tissue surrounding silicone breast implants. In sum, the adaptive B cell immune response to biomaterial depends on composition and induces local, regional and systemic immunological changes.

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Computational assignment of cell-cycle stage from single-cell transcriptome data

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