Biology subjects

Cherry, C.

Publications and source records attributed to Cherry, C..

21 records · Page 2Linked to original sources

bioRxiv2021

Age-related Immune-Stromal Networks Inhibit Response to Regenerative Immunotherapies

Aging is associated with immunological changes that compromise response to infections and vaccines, exacerbate inflammatory diseases and could potentially mitigate tissue repair. Even so, age-related changes to the immune response to tissue damage and regenerative medicine therapies remain unknown. Here, we characterized how aging induces senescence and immunological changes that inhibit tissue repair and therapeutic response to a clinical regenerative biological scaffold derived from extracellular matrix. Tissue signatures of inflammation and interleukin (IL)-17 signaling increased with injury and treatment in aged animals, and computational analysis uncovered age-associated senescent-T cell communication that promotes type 3 immunity in T cells. Local inhibition of type 3 immune activation using IL17-neutralizing antibodies improved healing and restored therapeutic response to the regenerative biomaterial, promoting muscle repair in older animals. These results provide insights into tissue immune dysregulation that occurs with aging that can be targeted to rejuvenate repair.

bioengineering↗

bioRxiv2020

Domino: reconstructing intercellular signaling dynamics with transcription factor activation in model biomaterial environments

Biomaterials serve as the basis of implants, tissue engineering scaffolds, and multiple other biomedical therapeutics. New technologies, such as single cell RNA sequencing (scRNAseq), are enabling characterization of the biomaterial response to an unprecedented level of detail, facilitating new discoveries in the complex cellular environment surrounding materials. We performed scRNAseq and integrated data sets from multiple experiments to create a single cell atlas of the biomaterials response that contains 42,156 cells from biological extracellular matrix (ECM)-derived and synthetic polyester (polycaprolactone, PCL) scaffold biomaterials implanted in murine muscle wounds. We identified 18 clusters of cells, including natural killer (NK) cells, multiple subsets of fibroblasts, and myeloid cells, many of which were previously unknown in the biomaterial response. To determine intra and intercellular signaling occurring between the numerous cell subsets, including immune-stromal interactions in the biomaterial response, we developed Domino (github.com/chris-cherry/domino), a computational tool which allows for identification of condition specific intercellular signaling patterns connected to transcription factor activation from single cell data. The Domino networks self-assembled into signaling modules and cellular subsets involved in signaling independent of clustering, defining interactions between immune, fibroblast, and tissue-specific modules with biomaterials-specific communication patterns. Further compilation and integration of biomaterials single cell data sets will delineate the impact of materials chemical and physical properties and biological factors, such as anatomical placement, age, or systemic disease, that will direct biomaterials design.

bioinformatics↗

bioRxiv2019

Single cell RNA-seq in regenerative and fibrotic biomaterial environments defines new macrophage subsets

Macrophages play diverse roles in the immune response to infection, cancer, and wound healing where they respond to local environmental signals, yet identification and phenotypic characterization of functional subsets in vivo remains limited. We performed single cell RNA sequencing analysis on differentiated macrophages sorted from a biologic matrix-induced regenerative environment versus a synthetic biomaterial foreign body response (FBR), characterized by TH2/interleukin (IL)-4 and TH17/IL-17, respectively. In the regenerative environment, unbiased clustering and pseudotime analysis revealed distinct macrophage subsets responsible for antigen presentation, chemoattraction, and phagocytosis, as well as a small population with expression profiles of both dendritic cells and skeletal muscle. In the FBR environment, we identified a CD9hi+IL-36{gamma}+ macrophage subset that expressed TH17-associated molecules characteristic of certain auto-immune responses that were virtually absent in mice lacking the IL-17 receptor. Surface marker combinations including CD9 and CD301b defined macrophage fibrotic and regenerative subsets enabling functional assessment and identification in human tissue. Application of the terminal macrophage subsets to train the SingleCellNet algorithm and comparison to human and mouse macrophages in tumor, lung, and liver suggest broad relevance of macrophage classification. These distinct macrophage subsets demonstrate previously unrecognized myeloid phenotypes involved in different tissue responses and provide new targets for potential therapeutic modulation of certain pathologic states and tissue repair.

immunology↗