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Biology subjects

Annels, N.

Publications and source records attributed to Annels, N..

2 recordsLinked to original sources

SpatioEv: Spatial evolution of protein and morphological features reveals development dynamics of cells and spatial neighbourhoods

Understanding cellular function in tissues demands sophisticated tools to decode complex microenvironmental interactions. Current spatial analysis methods often lack the comprehensive framework needed to systematically analyse cell morphology, dynamics, interactions, and extracellular matrix (ECM) architecture. We introduce SpatioEv, a unified computational framework for highly multiplexed tissue imaging that addresses these critical gaps. SpatioEv integrates automated quality control, cell phenotyping, neighbourhood identification, multi-scale spatial characterization, niche boundary analysis, ECM fiber-cell interaction mapping, and spatiotemporal trajectory inference. This pipeline enables reproducible cell annotation, reveals novel ECM-cell interactions, characterizes tissue neighbourhood boundaries, and infers developmental progressions directly from spatial data. Using this, we can identify disease-specific spatial signatures distinguishing rheumatoid arthritis from osteoarthritis, characterize diverse tumour boundary phenotypes in cancer metastases in liver, and map evolutionary trajectories in pancreatic ductal adenocarcinoma (PDAC) at single-niche resolution. Our findings highlight the significance of spatial context in shaping cell behaviour and underscore its potential to uncover emergent tissue architecture and cellular dynamics. By addressing major analytical challenges, SpatioEv provides a scalable, adaptable platform for advancing spatial biology and translational research.

systems biology↗

Diminished placental Factor XIIIA1 expression associates with long term ART and preterm birth in pregnant people living with HIV.

We previously showed a link between maternal vascular malperfusion and pre-term birth (PTB) in pregnant people living with HIV (PPLH) initiating antiretroviral treatment (ART) before pregnancy, indicating poor placental vascularisation. After measuring antenatal plasma angiogenic factors to seek mechanistic insights, low levels of plasma Factor XIIIA1 (FXIIIA1) and vascular-endothelial-growth-factor (VEGF) was significantly associated with PTB at the time closest to delivery (median 34 weeks) in PPLH initiating ART before pregnancy. Knowing that FXIIIA1 is crucial for haemostasis, angiogenesis, implantation and pregnancy maintenance and that expression is found on placental macrophages (Hofbauer cells), we examined placentae at delivery from matching participants who either initiating ART before pregnancy or during gestation. Highest FXIIIA1 expression was on Hofbauer cells but was significantly lower in PTB regardless of HIV infection, but was significantly lower in PPLH in PTB from women who initiated ART before pregnancy. To test the hypothesis that antiretroviral drugs may disrupt vascularisation in the placenta, we used a human umbilical vein endothelial cell (HUVEC) matrigel angiogenesis assay. We identified that addition of pre-treated FXIIIA1-expressing MCSF-and IL-10-induced placenta-like macrophages with physiological concentrations of tenofovir, 3TC, and efavirenz resulted in significantly inhibited angiogenesis; akin to the inhibition observed with titratable concentrations of ZED1301, an inhibitor of FXIIIA1. Overall, an efavirenz-containing ART combination inhibits vasculogenesis without causing toxicity and likely does so through inhibition of a FXIIIA1-mediated-placental macrophage pathway.

immunology↗