Biology subjects

Abbey, C. A.

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

3 recordsLinked to original sources

bioRxiv2026

A regenerative stem cell-derived matrix accelerates functional dermal wound repair in a diabetic model

Despite the growing prevalence of non-healing diabetic wounds, no current treatment options overcome multifactorial deficits in repair. To this end, a mesenchymal stromal cell-derived regenerative extracellular matrix (rECM) was evaluated for the ability to accelerate cutaneous wound repair in leptin receptor-deficient (db/db) diabetic mice with paired full-thickness dorsal skin defects. A single dose of rECM significantly accelerated wound closure compared with vehicle controls. Also, rECM dose-dependently improved overall histological healing scores and modulated granulation tissue dynamics, with the highest dose promoting rapid resolution of granulation tissue relative to wound area. Spatial transcriptomics and immunofluorescence revealed that rECM drove robust formation of de novo peripheral nerve clusters characterized by the Schwann cell marker, p75. The rECM also enhanced vascular maturation in healed wounds, increasing average blood vessel size, smooth muscle actin-positive vessels, and vessel density within myofibroblast-rich regions. In a complementary 3D angiogenic sprouting model, rECM accelerated endothelial invasion and filopodia extension, and at higher concentrations induced contraction of collagen matrices consistent with accelerated resolution of granulation tissue. These data demonstrate that rECM accelerates closure of diabetic skin defects by coordinating faster granulation tissue remodeling with enhanced peripheral nerve formation and vascular maturation.

physiology↗

bioRxiv2023

Identification of new markers of angiogenic sprouting using transcriptomics: New role for RND3

BackgroundNew blood vessel formation requires endothelial cells to transition from a quiescent to an invasive phenotype. Transcriptional changes are vital for this switch, but a comprehensive genome-wide approach focused exclusively on endothelial cell sprout initiation has not been reported. Approach and ResultsUsing a model of human endothelial cell sprout initiation, we developed a protocol to physically separate cells that initiate the process of new blood vessel formation (invading cells) from non-invading cells. We used this model to perform multiple transcriptomics analyses from multiple donors to monitor endothelial gene expression changes. Single-cell Population Analyses, single-cell Cluster Analyses, and bulk RNA sequencing were used to delineate transcriptomic changes in invading cells. The results revealed a 39 gene signature that was consistent with activation of signal transduction, morphogenesis, and immune responses. Many of the genes were previously shown to regulate angiogenesis, and include multiple tip cell markers. Upregulation of SNAI1, PTGS2, and JUNB protein expression was confirmed in invading cells, and silencing JunB and SNAI1 significantly reduced invasion responses. Separate studies investigated Rounding 3 (RND3), also known as RhoE, which has not yet been implicated in angiogenesis. Silencing RND3 reduced endothelial invasion distance as well as filopodia length, fitting with a pathfinding role for RND3 via regulation of filopodial extensions. Analysis of in vivo retinal angiogenesis in Rnd3 heterozygous mice confirmed a decrease in filopodial length compared to wild type littermates. ConclusionValidation of multiple genes, including RND3, revealed a functional role for this gene signature early in the angiogenic process. This study expands the list of genes that are associated with the acquisition of a tip cell phenotype during endothelial cell sprout initiation. HIGHLIGHTSO_LITranscriptomic analyses identified 39 candidate genes that were upregulated at the onset of endothelial sprouting C_LIO_LIThe gene signature includes signal transduction, morphogenesis, and immune responses C_LIO_LINewly-identified RND3 is associated with filopodial extension and pathfinding C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/563021v1_ufig1.gif" ALT="Figure 1"> View larger version (92K): org.highwire.dtl.DTLVardef@1045439org.highwire.dtl.DTLVardef@1357703org.highwire.dtl.DTLVardef@1189cf2org.highwire.dtl.DTLVardef@e7d574_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2022

Annexin A2 modulates phospholipid membrane composition upstream of Arp2 to control angiogenic sprout initiation

The intersection of protein and lipid biology is of growing importance for understanding how cells address structural challenges during adhesion and migration. While protein complexes engaged with the cytoskeleton play a vital role, support from the phospholipid membrane is crucial for directing localization and assembly of key protein complexes. During angiogenesis, it is well observed that dramatic cellular remodeling is necessary for endothelial cells to shift from a stable monolayer to invasive structures. However, the molecular dynamics between lipids and proteins during endothelial invasion are not defined. Here, we utilized cell culture, immunofluorescence, and lipidomic analyses to identify a novel role for the membrane binding protein Annexin A2 (ANXA2) in modulating the composition of specific membrane lipids necessary for cortical F-actin organization and adherens junction stabilization. In the absence of ANXA2, there is disorganized cortical F-actin, reduced junctional Arp2, excess sprout initiation, and ultimately failed sprout maturation. Further, we observed reduced filipin III labeling of membrane cholesterol in cells with reduced ANXA2, suggesting there is an alteration in phospholipid membrane dynamics. Lipidomic analyses reveal that 42 lipid species are altered with loss of ANXA2, including an accumulation of phosphatidylcholine (16:0_16:0). We find that supplementation of phosphatidylcholine (16:0_16:0) in wild-type endothelial cells mimics the ANXA2 knock-down phenotype, indicating that ANXA2 regulates the phospholipid membrane upstream of Arp2 recruitment and organization of cortical F-actin. Altogether these data indicate a novel role for ANXA2, and show that proper lipid modulation is a critical component of endothelial sprouting. Summary StatementAnnexin A2 modulates composition of select phospholipid species in endothelial cells needed for F-actin organization and Arp2 recruitment to endothelial adherens junctions. These events simultaneously temper sprout initiation and support sprout maturation to maintain the integrity of sprouting structures during angiogenesis

cell biology↗