Biology subjects

Schmoeckel, E.

Publications and source records attributed to Schmoeckel, E..

4 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

Comparative single-cell atlases reveal injury-driven tubal epithelial regeneration as a window for ovarian carcinoma initiation

High-grade serous carcinoma (HGSC), the most lethal form of ovarian cancer, preferentially originates in the tubal epithelium (TE) of the distal uterine tube (also known as Fallopian tube or oviduct). Mouse models are widely used to study how HGSC initiates in humans; however, the extent to which mouse and human uterine tubes are comparable remains unclear. Here, we conduct cross-species single-cell transcriptomic comparative analyses and organoid assay validations to reveal conserved differentiation trajectories from bipotent progenitors to secretory or ciliated cell fates. Regional analyses of both datasets reveal enriched injury repair features in the distal human TE, where mice lack such a trend. Experimentally inducing mechanical injury to the mouse TE yields significant expansion of pre-ciliated cells compared to uninjured counterparts. Furthermore, inactivation of Trp53 and Rb1, whose pathways are commonly altered in HGSC, in regenerating pre-ciliated cells leads to rapid neoplastic transformation, implicating post-traumatic repair as a permissive window for malignant transformation. Together, our findings establish a comparative atlas of cell states between mice and humans, show that injury-associated regeneration may contribute to the known vulnerability of the fimbrial region, and raise potential concerns regarding procedures or conditions that mechanically perturb the tubal epithelium.

cancer biology↗

bioRxiv2026

Keratin 5 marks cancer-propagating cells sustained by an osteopontin-producing niche in high-grade serous ovarian carcinoma

High-grade serous carcinoma (HGSC) is the most common and aggressive form of ovarian cancer. Advanced HGSCs exhibit pronounced cellular heterogeneity, including a subset of cancer-propagating cells (CPCs, also known as cancer stem cells) that are highly tumorigenic and display stem cell-associated properties such as self-renewal and chemoresistance. In contrast, a substantial fraction of HGSC cells is non-tumorigenic. The role of these non-cancer-propagating cells (non-CPCs) and their relationship to CPCs remain poorly understood. Here, we demonstrate that neoplastic cells expressing the intermediate filament protein keratin 5 (KRT5) represent bona fide CPCs. KRT5 cells form cancer organoids over successive passages, are tumorigenic in serial dilution xenograft assays, and are resistant to the antineoplastic agents, doxorubicin and cisplatin. Single-cell lineage-tracing experiments show that KRT5 CPCs give rise to KRT5- cells. KRT5 and KRT5- populations exhibit distinct gene expression profiles, with KRT5- cells characterized by expression of SPP1, which encodes the secreted factor osteopontin (OPN). Treatment with OPN enhances HGSC organoid growth and chemoresistance, whereas SPP1 knockdown reverses these effects. Together, these findings support a model in which HGSC contains two hierarchically related cell populations: KRT5, OPN-responsive CPCs and KRT5-, non-tumorigenic cells that form a niche producing OPN. Targeting pathways that sustain both stem-like tumor cells and their supportive niche may enable reduced dosing of highly toxic chemotherapeutic agents while enhancing therapeutic efficacy in HGSC.

cancer biology↗

bioRxiv2023

Plant geographic distribution influences chemical defenses in native and introduced Plantago lanceolata populations

Plants growing outside their native range may be confronted by new regimes of herbivory, but how this affects plant chemical defense profiles has rarely been studied. Using Plantago lanceolata as a model species, we investigated whether introduced populations show significant differences from native populations in several growth and chemical defense traits. Plantago lanceolata (ribwort plantain) is an herbaceous plant species native to Europe and Western Asia that has been introduced to numerous countries worldwide. We sampled seeds from nine native and ten introduced populations that covered a broad geographic and environmental range and performed a common garden experiment in a greenhouse, in which we infested half of the plants in each population with caterpillars of the generalist herbivore Spodoptera littoralis. We then measured size-related and resource-allocation traits as well as the levels of constitutive and induced chemical defense compounds in roots and shoots of P. lanceolata. When we considered the environmental characteristics of the site of origin, our results revealed that populations from introduced ranges were characterized by an increase of chemical defense compounds without compromising plant biomass. The concentrations of iridoid glycosides and verbascoside, the major anti-herbivore defense compounds of P. lanceolata, were higher in introduced populations than in native populations. In addition, introduced populations exhibited greater rates of herbivore-induced volatile organic compound emission and diversity, and similar chemical diversity based on untargeted analyses of leaf methanol extracts. In general, the geographic origin of the populations had a significant influence on morphological and chemical plant traits, suggesting that P. lanceolata populations are not only adapted to different environments in their native range, but also in their introduced range.

ecology↗