Mora-Roldan, G. A. | bioRxiv Science

bioRxiv2026

Engineered trophoblast organoids recapitulate molecular and functional features of preeclampsia

Preeclampsia is a major pregnancy complication driven by placental dysfunction, yet research is limited by reliance on patient-derived tissues and models that do not fully capture human disease. Here, we develop a genetically engineered human trophoblast organoid model of preeclampsia that can be generated without access to placental tissue. Using a CRISPR-based Prime Integrase strategy, we engineered induced trophoblast stem cells to express the preeclampsia-associated soluble fms-like tyrosine kinase-1 (sFlt-1) exon 15a isoform. Engineered organoids showed a transcriptional shift towards primary preeclamptic placentae and developed several features of disease. These included reduced PlGF, increased IL-6 and soluble endoglin, oxidative stress, impaired growth and an elevated sFlt-1/PlGF ratio comparable to primary preeclamptic trophoblast organoids. These broader changes were not reproduced by adding recombinant human sFlt-1 to control organoids. Conditioned media from engineered organoids impaired endothelial network formation, demonstrating a functional effect of the altered trophoblast secretome. Treatment with sulfasalazine and metformin also restored angiogenic balance and organoid growth. Together, these findings establish a tractable human model that reproduces molecular and functional features of preeclampsia and provides a platform to study disease mechanisms and test potential therapies.

cell biology↗

bioRxiv2024

STAMP: Single-Cell Transcriptomics Analysis and Multimodal Profiling through Imaging

We introduce Single-Cell Transcriptomics Analysis and Multimodal Profiling (STAMP), a scalable profiling approach of individual cells. Leveraging transcriptomics and proteomics imaging platforms, STAMP eliminates sequencing costs, to enable single-cell genomics from hundreds to millions of cells at an unprecedented low cost. Stamping cells in suspension onto imaging slides, STAMP supports single-modal (RNA or protein) and multimodal (RNA and protein) profiling and flexible, ultra-high-throughput formats. STAMP allows the analysis of a single or multiple samples within the same experiment, enhancing experimental flexibility, throughput and scale. We tested STAMP with diverse sample types, including peripheral blood mononuclear cells (PBMCs), dissociated cancer cells and differentiated embryonic stem cell cultures, as well as whole cells and nuclei. Combining RNA and protein profiling, we applied immuno-phenotyping of millions of blood cells simultaneously. We also used STAMP to identify ultra-rare cell populations, simulating clinical applications to identify circulating tumor cells (CTCs). Performing in vitro differentiation studies, we further showed its potential for large-scale perturbation studies. Together, STAMP establishes a new standard for cost-effective, scalable single-cell analysis. Without the need for sequencing, STAMP makes high-resolution profiling more affordable and accessible. Designed to meet the needs of research labs, diagnostic cores and pharmaceutical companies, STAMP holds the promise to transform our capacity to map human biology, diagnose diseases and drug discovery.

genomics↗