Biology subjects

McKinnon, B.

Publications and source records attributed to McKinnon, B..

4 recordsLinked to original sources

bioRxiv2025

Molecular signature of human endometrial stem/progenitor cells at the single cell level

Human endometrium sheds and regenerates each month during the menstrual cycle. N-cadherin+ (CDH2) glandular epithelial progenitors and SUSD2+ MSC and their niches have been identified but their signaling interactions remain unknown. SSEA1+ epithelial cells resurface the endometrium generating a new luminal epithelium each cycle. Based on these markers, we characterised the gene expression of human endometrial stem/progenitor cell-enriched populations derived from FACSorted hysterectomy endometrium by scRNAseq. Two of 10 epithelial clusters contained CDH2+SOX9+ cells with high TRH and IHH expression. N-cadherin and IHH, and SSEA1 and Hedgehog coreceptor BOC immunocolocalised in the basal layer of endometrial glands from which the new functional layer glands regenerate each menstrual cycle. Two of six mesenchymal clusters contained SUSD2+ MSC, one with high MUSTN1 expression. Epithelial progenitors and endometrial MSC transitioned to their respective progeny. We provide new insights into human endometrial stem/progenitor cell signaling pathways and niche interactions regulating their function. HighlightsO_LIEnriching cell suspensions of human endometrial cells from hysterectomy tissues with CDH2+ epithelial progenitors, SSEA-1+ basalis epithelial cells and SUSD2+ perivascular MSC enabled their gene profiling at the single cell level. C_LIO_LIMultiple cell fate trajectory analyses showed that CDH2+SOX9+ epithelial cells and SUSD2+MYH11+MCAM+MUSTN1+ MSC are the progenitors for human endometrial glandular and luminal epithelial cells, and stromal vascular cells, respectively. C_LIO_LIEnriched TRH expression in human endometrial epithelial progenitors suggests a role in their progenitor function. C_LIO_LIInteraction between IHH of SOX9+ human endometrial epithelial progenitors with basalis fibroblasts and decidualized stroma and co-receptor BOC suggests IHH signalling may have a role in basalis epithelial migration to repair the luminal epithelium during menses. C_LI eTOC blurbGargett and colleagues provide a molecular signature of human endometrial stem/progenitor cells by enriching 4 stem/progenitor populations from hysterectomies using known markers for scRNAseq analysis. The two epithelial and two MSC progenitor states identified transitioned to their differentiated progeny. IHH was validated as a key signalling molecule of epithelial progenitors in basal glands that interacted with BOC co-receptors.

molecular biology↗

bioRxiv2025

Mechanism of Nanomaterial-Induced Lipid Droplet Formation in Raphidocelis subcapitata is Mediated by Charge Properties

Increasing the production of renewable energy will be critical to achieving global sustainability goals in the coming decades. Biofuels derived from microalgae have great potential to contribute to this production. However, cultivating algae with sufficient neutral lipid content, while maintaining high growth rates, is a continual challenge in making algal-derived biofuels a reality. Previous work has shown that exposure to polymer-functionalized carbon dots can increase the lipid content of the microalgae Raphidocelis subcapitata. This study investigates this finding, aiming to determine the mechanisms underlying this effect and if altering nanoparticle surface charge mediates the mechanism of action of the carbon dots used. Carbon dots with both negative and positive surface charges were added to microalgal cultures, and the impacts of this exposure were analyzed using high-content imaging, growth measurements, and chlorophyll content measurements. Results indicate that positively charged carbon dots induce a nano-specific increase in lipid content but also cause decreases in growth. Additionally, the mechanism of action of each nanoparticle was examined by conducting a morphological comparison to known treatments. This analysis showed that negatively charged carbon dots cause similar impacts to R. subcapitata as nitrogen deprivation, a known mechanism by which lipid droplet content can be increased. The findings of this study suggest that carbon dots may have surface charge dependent effects on the lipid metabolism of R. subcapitata. Future work should consider the use of carbon dots with varied surface charge densities for enhancing algae biofuel production in bioreactors.

plant biology↗

bioRxiv2024

M2 Macrophages are Major Mediators of Germline Risk of Endometriosis and Explain Pleiotropy with Comorbid Traits

Endometriosis is a common gynecologic condition that causes chronic life-altering symptoms including pain, infertility, and elevated cancer risk. There is an urgent need for new non-hormonal targeted therapeutics to treat endometriosis, but until very recently, the cellular and molecular signatures of endometriotic lesions were undefined, severely hindering the development of clinical advances. Integrating inherited risk data from analyses of >450,000 individuals with [~]350,000 single cell transcriptomes from 21 patients, we uncover M2-macrophages as candidate drivers of disease susceptibility, and nominate IL1 signaling as a central hub impacted by germline genetic variation associated with endometriosis. Extensive functional follow-up confirmed these associations and revealed a pleiotropic role for this pathway in endometriosis. Population-scale expression quantitative trail locus analysis demonstrated that genetic variation controlling IL1A expression is also associated with endometriosis risk variants. Manipulation of IL1 signaling in state-of-the-art in vitro decidualized assembloids impacted epithelial differentiation, and in an in vivo endometriosis model, treatment with anakinra (an interleukin-1 receptor antagonist) resulted in a significant, dose-dependent reduction in both spontaneous pain and evoked pain. Together these studies highlight non-diagnostic cell types as central to endometriosis susceptibility and support IL1 signaling as an important actionable pathway for this disease.

immunology↗

bioRxiv2024

Tracing Endometriosis: Coupling deeply phenotyped, single-cell based Endometrial Differences and AI for disease pathology and prediction

Endometriosis, affecting 1 in 9 women, presents treatment and diagnostic challenges. To address these issues, we generated the biggest single-cell atlas of endometrial tissue to date, comprising 466,371 cells from 35 endometriosis and 25 non-endometriosis patients without exogenous hormonal treatment. Detailed analysis reveals significant gene expression changes and altered receptor-ligand interactions present in the endometrium of endometriosis patients, including increased inflammation, adhesion, proliferation, cell survival, and angiogenesis in various cell types. These alterations may enhance endometriosis lesion formation and offer novel therapeutic targets. Using ScaiVision, we developed neural network models predicting endometriosis of varying disease severity (median AUC = 0.83), including an 11-gene signature-based model (median AUC = 0.83) for hypothesis-generation without external validation. In conclusion, our findings illuminate numerous pathway and ligand-receptor changes in the endometrium of endometriosis patients, offering insights into pathophysiology, targets for novel treatments, and diagnostic models for enhanced outcomes in endometriosis management.

molecular biology↗