Biology subjects

Herse, F.

Publications and source records attributed to Herse, F..

3 recordsLinked to original sources

bioRxiv2025

OpenDVP: An experimental and computational framework for community-empowered deep visual proteomics

Deep visual proteomics (DVP) is an emerging approach for cell type-specific and spatially resolved proteomics. However, its broad adoption has been constrained by the lack of an open-source end-to-end workflow in a community-driven ecosystem. Here, we introduce openDVP, an experimental and computational framework for simplifying and democratizing DVP. OpenDVP integrates open-source software for image analysis, including MCMICRO, QuPath, and Napari, and uses the scverse data formats AnnData and SpatialData for multi-omics integration. It offers two workflows: a fast-track pipeline requiring no image analysis expertise and an artificial intelligence (AI)-powered pipeline with recent algorithms for image pre-processing, segmentation, and spatial analysis. We demonstrate openDVPs versatility in three archival tissue studies, profiling human placenta, early-stage lung cancer, and locally relapsed breast cancer. In each study, our framework provided insights into health and disease states by integrating spatial single-cell phenotypes with exploratory proteomic data. Finally, we introduce deep proteomic profiling of cellular neighborhoods as a scalable approach to accelerate spatial discovery proteomics across biological systems.

systems biology↗

bioRxiv2025

Maternal smoking in early pregnancy disrupts placental function through syncytiotrophoblast and macrophage dysregulation.

Smoking in pregnancy is the leading avoidable cause of gestational morbidity and mortality, causally linked to fetal growth restriction (FGR). The placenta, functional interface between mother and fetus is essential for healthy fetal development. For the first time, we studied cell type-resolved smoking effects on placental development at high molecular resolution using single-nucleus RNA sequencing and deep visual proteomics of matched tissues. We validated our findings through an independent cohort and in-vitro cigarette smoke exposure to primary human trophoblast cells. Our results show placental macrophages (Hofbauer cells; HBC) and the syncytiotrophoblast (STB) barrier are most affected by smoking, with dysregulation of cell-cell adhesion, extracellular matrix organization, and stress phenotype. STBs show moderate compositional increases in smokers and in-silico trophoblast differentiation modelling indicates a preferential shift towards the STB lineage in this group. The trophoblast displays a large upregulation of pro-angiogenic effectors, increases in xenobiotic detoxification, reduced mitochondrial function, and vastly altered transmembrane transport. These molecular changes affect placental development with important consequences for fetal growth. We provide insight into placental dysfunction contributing to FGR early in pregnancy, before clinical symptoms appear. We anticipate this data to advance diagnostics and therapies to improve FGR outcomes.

systems biology↗

bioRxiv2022

Disturbed trophoblast transition links preeclampsia progression from placenta to the maternal syndrome

Pre-eclampsia (PE) is a syndrome that affects multiple organ systems and is the most severe hypertensive disorder in pregnancy. It frequently leads to preterm delivery, maternal and fetal morbidity and mortality and life-long complications1. We currently lack efficient screening tools2, 3 and early therapies4, 5 to address PE. To investigate the early stages of early onset PE, and identify candidate markers and pathways, we performed spatio-temporal multi-omics profiling of human PE placentae and healthy controls and validated targets in early gestation in a longitudinal clinical cohort. We used a single-nuclei RNA-seq approach combined with spatial proteo- and transcriptomics and mechanistic in vitro signalling analyses to bridge the gap from late pregnancy disease to early pregnancy pathomechanisms. We discovered a key disruption in villous trophoblast differentiation, which is driven by the increase of transcriptional coactivator p300, that ultimately ends with a senescence-associated secretory phenotype (SASP) of trophoblasts. We found a significant increase in the senescence marker activin A in preeclamptic maternal serum in early gestation, before the development of clinical symptoms, indicating a translation of the placental syndrome to the maternal side. Our work describes a new disease progression, starting with a disturbed transition in villous trophoblast differentiation. Our study identifies potential pathophysiology-relevant biomarkers for the early diagnosis of the disease as well as possible targets for interventions, which would be crucial steps toward protecting the mother and child from gestational mortality and morbidity and an increased risk of cardiovascular disease later in life.

systems biology↗