Biology subjects

Morris, C. A.

Publications and source records attributed to Morris, C. A..

3 recordsLinked to original sources

bioRxiv2026

Temporal and Age-Dependent Regulation of Phagocytosis-Related Signatures After Ischemic Stroke: Cross-Species Transcriptomic Evidence

BackgroundEfferocytosis, the phagocytic clearance of apoptotic and damaged cells, promotes inflammation resolution and tissue repair following ischemic stroke. This study investigated temporal changes in efferocytosis and phagocytosis-related transcriptional programs during acute experimental stroke, examined the effects of aging on these responses, and assessed whether similar immune signatures are present in human ischemic stroke. MethodsPublicly available transcriptomic datasets from murine transient middle cerebral artery occlusion (tMCAO; GSE104036 and GSE112348), permanent middle cerebral artery occlusion (pMCAO; GSE137482), and human peripheral blood after ischemic stroke (GSE16561) were analyzed using OmicSoft/Ingenuity-style pathway analysis. Functional validation included in vivo assessment of efferocytosis after tMCAO and in vitro phagocytosis assays using bone marrow-derived macrophages from young and aged mice. ResultsBoth acute tMCAO models exhibited robust inflammatory activation together with sustained activation of phagocyte-related pathways during the first 24 hours after stroke. Human peripheral blood demonstrated similar inflammatory and phagocytic signatures, supporting translational relevance. Increased efferocytosis at 24 hours after tMCAO was associated with neuroprotection. Although both young and aged mice activated phagocytosis-related pathways after pMCAO, aged mice showed reduced phagosome formation. Consistent with these findings, macrophages from aged mice exhibited enhanced inflammatory responses and impaired uptake of apoptotic cells. ConclusionsA conserved post-stroke immune response characterized by inflammatory activation and phagocyte-mediated clearance was identified across murine and human datasets. Efficient efferocytosis was associated with neuroprotection, whereas aging impaired apoptotic cell clearance and promoted a pro-inflammatory macrophage phenotype, highlighting efferocytosis as a potential therapeutic target for ischemic stroke.

neuroscience↗

bioRxiv2026

AnchorR: A QuPath and R interface for collaborative exploration of spatial transcriptomics and histology

Single-cell spatial transcriptomics can connect molecular cell states with tissue morphology, but this promise depends on accurate registration to histopathology. In serial sections, however, tissue borders often differ because of sectioning artifacts, staining variability, and field-of-view acquisition, limiting conventional area-based registration. We developed AnchorR, an expert-guided workflow for coarse-grained alignment of hematoxylin and eosin (H&E) images with CosMx Spatial Molecular Imaging data. Bioinformaticians first define and color-code cell types in Seurat, and pathologists then identify corresponding internal landmarks using QuPath overlays. AnchorR combines these paired landmarks to estimate affine transformations, quantify residual error, and support visual quality control and anchor refinement. Using six oral pre-cancerous tissue sections, we identified 60 cross-modal landmarks. Fitting each section independently reduced mean landmark error from 121.5 m with a single whole-slide transformation to 14.6 m. Cross-validation further showed that increasing the number of anchors improved robustness, with nine-anchor fits achieving approximately 20 m error, or about one cell diameter. AnchorR is designed to complement automated computer-vision methods by providing reliable tissue-level alignment when border mismatch makes global registration difficult. By creating a shared workspace for pathologists and bioinformaticians, it operationalizes an expert-in-the-loop approach and makes feature-based multimodal registration accessible without specialized computer-vision expertise or high-performance computing.

bioinformatics↗

bioRxiv2024

Epigenetic restoration of differentiation competency via reversal of epiblast regionalisation

Although the epiblast in the embryo has the capacity to generate all tissues of the body, its in vitro counterparts often exhibit differentiation biases, posing significant challenges for both basic research and translational applications involving pluripotent stem cells (PSCs). The origins of these biases remain incompletely understood. In this study, we identify PSC differentiation biases as arising from fluctuations in repressive and activating histone posttranslational modifications, leading to the acquisition of a caudal epiblast-like phenotype. We present a novel approach to overcome this bias using a chemical chromatin restoration (CHR) treatment. This method restores transcriptional programs, chromatin accessibility, histone modification profiles, and differentiation potential, effectively recapitulating the competent anterior epiblast-like state. Furthermore, we propose that a high bivalency state is a defining feature of the anterior human epiblast. We suggest that fluctuations in histone modification marks drive epiblast regionalization, ultimately shaping cellular responses to differentiation cues.

developmental biology↗