Biology subjects

Pirtz, M. G.

Publications and source records attributed to Pirtz, M. G..

3 recordsLinked to original sources

bioRxiv2026

Cross-species analysis links cell-cell communication rewiring to NOTCH2 during serous endometrial carcinogenesis

Cell-cell interactions shape the fate of mutant cells during cancer initiation but how these interactions evolve during progression to pathologically recognizable lesions remain poorly understood. Here, we investigated cell-cell communication during serous endometrial carcinoma (SEC; also known as uterine serous carcinoma) development using a lineage-traceable mouse model and cross-species analyses of the mouse and human neoplastic endometrium. In mice, the early, pre-dysplastic stage was marked by a global decrease in inferred cell-cell interactions, followed by extensive communication network rewiring during neoplastic progression. Pathway-specific analysis revealed a similar pattern for NOTCH signaling, with NOTCH2 emerging as the dominant NOTCH receptor in Trp53/Rb1-mutant immature epithelial cells. Functionally, NOTCH2 promoted the outgrowth of more proliferative mutant organoids. Cross-species transcriptomic analysis identified conserved immature epithelial states in mouse and human neoplastic endometrial epithelium. In human tissues, NOTCH2 was overexpressed in serous endometrial intraepithelial carcinoma, a precursor of SEC, and in overt SEC. Furthermore, elevated NOTCH2 expression was associated with poor patient survival. These findings link cell-cell communication rewiring during experimental SEC development to conserved neoplastic epithelial states and identify NOTCH2 as an early marker and a potential target of disease interception.

cancer biology↗

bioRxiv2026

Shape Factor Analysis as a Quantitative Framework for Assessing Spheroid and Organoid Morphology and Invasiveness

Morphological changes of spheroids and organoids are widely used as in vitro indicators of healthy and diseased tissue functions; however, quantitative methods to classify spheroid and organoid morphology are limited. In clinical breast imaging, radiologists use tumor shape as a prognostic marker, with irregular margins associated with invasive disease and increased malignancy. Here, we adapted this approach for translational research and developed a custom MATLAB algorithm to quantify the variance in radial lengths of invasive protrusions in spheroids and organoids. First, we analyzed digital phantoms by both ImageJ/FIJI shape descriptors and our radial length analysis to evaluate the capabilities of each measurement method. Subsequently, we performed the same comparisons with images from experimental spheroid and organoid datasets. We demonstrate that multivariate shape factor analysis, including radial length analysis, enables more reliable and comprehensive quantification of spheroid and organoid morphologies than standard shape descriptors alone. By enabling numerical morphological readouts, shape factor analysis can enhance phenotypic profiling of spheroids and organoids and provide valuable metrics for in vitro studies including high-throughput and drug screening workflows.

bioengineering↗

bioRxiv2024

Dysregulation of cell state dynamics during early stages of serous endometrial carcinogenesis

Serous endometrial carcinoma (SEC) constitutes about 10% of endometrial carcinomas and is one of the most aggressive and lethal types of uterine cancer. Due to the rapid progression of SEC, early detection of this disease is of utmost importance. However, molecular and cellular dynamics during the pre-dysplastic stage of this disease remain largely unknown. Here, we provide a comprehensive census of cell types and their states for normal, pre-dysplastic, and dysplastic endometrium in a mouse model of SEC. This model is associated with inactivation of tumor suppressor genes Trp53 and Rb1, whose pathways are altered frequently in SEC. We report that pre-dysplastic changes are characterized by an expanded and increasingly diverse immature luminal epithelial cell populations. Consistent with transcriptome changes, cells expressing the luminal epithelial marker TROP2 begin to substitute FOXA2+ cells in the glandular epithelium. These changes are associated with a reduction in number and strength of predicted interactions between epithelial and stromal endometrial cells. By using a multi-level approach combining single-cell and spatial transcriptomics paired with screening for clinically relevant genes in human endometrial carcinoma, we identified a panel of 44 genes suitable for further testing of their validity as early diagnostic and prognostic markers. Among these genes are known markers of human SEC, such as CDKN2A, and novel markers, such as OAS2 and OASL, members of 2-5A synthetase family that is essential for the innate immune response. In summary, our results suggest an important role of the luminal epithelium in SEC pathogenesis, highlight aberrant cell-cell interactions in pre-dysplastic stages, and provide a new platform for comparative identification and characterization of novel, clinically relevant prognostic and diagnostic markers and potential therapeutic modalities.

cancer biology↗