Biology subjects

Plazyo, O.

Publications and source records attributed to Plazyo, O..

4 recordsLinked to original sources

bioRxiv2025

VGLL3-centered network connects placental, vascular, and immune defects in preeclampsia

Preeclampsia affects approximately 1 in 10 pregnancies, leading to severe complications and long-term health risks for both mother and offspring. While the etiology remains unclear, preeclampsia has been linked to both autoimmunity and the timing of menarche. Through human single-cell and spatial analyses, coupled with in vitro, in vivo, and ex vivo models, we demonstrate that VGLL3, a transcription co-regulator in the Hippo pathway, is upregulated in preeclamptic placentas. VGLL3 promotes immune activation, impairs trophoblast differentiation, and induces endothelial dysfunction, all of which contribute to pregnancy-related hypertension, fetal growth restriction, and offspring mortality. Our data reveal that VGLL3 acts upstream of preeclampsia-associated processes, including the production of sFLT1, a key biomarker of the disease. Notably, targeting VGLL3--either by genetic deletion in mouse placentas or through therapeutic inhibition in human placentas--protects against preeclampsia and alleviates disease pathology. These findings position VGLL3 as a promising novel therapeutic target for preeclampsia.

immunology↗

bioRxiv2025

Seq-Scope-eXpanded: Spatial Omics Beyond Optical Resolution

Sequencing-based spatial transcriptomics (sST) enables transcriptome-wide gene expression mapping but falls short of reaching the optical resolution (200-300 nm) of imaging-based methods. Here, we present Seq-Scope-X (Seq-Scope-eXpanded), which empowers submicrometer-resolution Seq-Scope with tissue expansion to surpass this limitation. By physically enlarging tissues, Seq-Scope-X minimizes transcript diffusion effects and increases spatial feature density by an additional order of magnitude. In liver tissue, this approach resolves nuclear and cytoplasmic compartments in nearly every single cell, uncovering widespread differences between nuclear and cytoplasmic transcriptome patterns. Independently confirmed by imaging-based methods, these results suggest that individual hepatocytes can dynamically switch their metabolic roles. Seq-Scope-X is also applicable to non-hepatic tissues such as brain and colon, and can be modified to perform spatial proteomic analysis, simultaneously profiling hundreds of barcode-tagged antibody stains at microscopic resolutions in mouse spleens and human tonsils. These findings establish Seq-Scope-X as a transformative tool for ultra-high-resolution whole-transcriptome and proteome profiling, offering unparalleled spatial precision and advancing our understanding of cellular architecture, function, and disease mechanisms.

genomics↗

bioRxiv2021

Non-lesional and Lesional Lupus Skin Share Inflammatory Phenotypes that Drive Activation of CD16+ Dendritic Cells

Cutaneous lupus erythematosus (CLE) is a disfiguring and poorly understood condition frequently associated with systemic lupus. Studies to date suggest that non-lesional keratinocytes play a role in disease predisposition, but this has not been investigated in a comprehensive manner or in the context of other cell populations. To investigate CLE immunopathogenesis, normal-appearing skin, lesional skin, and circulating immune cells from lupus patients were analyzed via integrated single-cell RNA-sequencing and spatial-seq. We demonstrate that normal-appearing skin of lupus patients represents a type I interferon-rich, prelesional environment that skews gene transcription in all major skin cell types and dramatically distorts cell-cell communication. Further, we show that lupus-enriched CD16+ dendritic cells undergo robust interferon education in the skin, thereby gaining pro-inflammatory phenotypes. Together, our data provide a comprehensive characterization of lesional and non-lesional skin in lupus and identify a role for skin education of CD16+ dendritic cells in CLE pathogenesis.

immunology↗

bioRxiv2020

Single Cell and Spatial Transcriptomics Defines the Cellular Architecture of the Antimicrobial Response Network in Human Leprosy Granulomas

Granulomas are complex cellular structures comprised predominantly of macrophages and lymphocytes that function to contain and kill invading pathogens. Here, we investigated single cell phenotypes associated with antimicrobial responses in human leprosy granulomas by applying single cell and spatial sequencing to leprosy biopsy specimens. We focused on reversal reactions (RR), a dynamic process in which some patients with disseminated lepromatous leprosy (L-lep) transition towards self-limiting tuberculoid leprosy (T-lep), mounting effective antimicrobial responses. We identified a set of genes encoding proteins involved in antimicrobial responses that are differentially expressed in RR versus L-lep lesions, and regulated by IFN-{gamma} and IL-1{beta}. By integrating the spatial coordinates of the key cell types and antimicrobial gene expression in RR and T-lep lesions, we constructed a map revealing the organized architecture of granulomas depicting compositional and functional layers by which macrophages, T cells, keratinocytes and fibroblasts contribute to the antimicrobial response.

immunology↗