Biology subjects

Dell, C. W.

Publications and source records attributed to Dell, C. W..

3 recordsLinked to original sources

bioRxiv2026

NucleoNet and DropNet: Generalist deep learning models for instance segmentation of nuclei and lipid droplets from electron microscopy images

Automating cellular organelle segmentation is key to increasing the throughput in electron microscopy (EM) and volume EM (vEM) workflows. Deep learning (DL) has accelerated this process, but model development has predominately centered on mitochondria, partly because of a scarcity of suitable training datasets for other features. Here, we crowdsourced the manual step of labeling nuclei and lipid droplets (LDs) from complex cellular EM images and trained Panoptic DeepLab (PDL) models on these large, heterogenous annotated datasets as well as on publicly available vEM datasets. NucleoNet and DropNet, the resulting instance segmentation models for nuclei and LDs, respectively, yield high-quality results on varied benchmarks. We applied these models to quantify differences between 2D and 3D in vitro cancer models versus in vivo tumors, highlighting a path toward robust quantitation in EM. NucleoNet and DropNet are publicly available on our napari plugin, empanada v1.2, for easy point-and-click segmentation of 2D and 3D cellular EM images.

cell biology↗

bioRxiv2025

A simple liquid 3D cell culture paradigm models oxidative mitochondrial metabolism of epithelial breast cancer cells with relevance for lung metastases.

Three-dimensional (3D) cell culture systems have emerged as powerful tools for modeling tumor biology in ex vivo settings. However, the diverse array of available 3D culture methods presents challenges in selecting the most appropriate model for specific research questions. This study provides a comparative analysis of breast cancer cells (SUM149, IBC-3, and MDA-MB-468) in the mammosphere culture (SphC) model or an "emboli" culture (EmC) model, which enrich for cancer stem cells and epithelial features, respectively. The EmC model, designed originally for inflammatory breast cancer, is characterized by media viscosity and mechanical rocking of the culture vessel. Notably, cells in EmC showed a distinct and durable reduction in cell proliferation ex vivo while demonstrating increased capacity to establish experimental lung metastases in vivo. Ultrastructural quantitative analysis of electron microscopy images suggested that cells in EmC acquire nuclear and mitochondrial features that resemble those of tumor tissue. Proteomics, single-cell transcriptomics, and metabolic flux analyses showed that cells in EmC and SphC favor mitochondrial oxidative metabolism (OXPHOS) and glycolysis, respectively. EmC rendered cells hypersensitive to OXPHOS inhibition, but more resistant to oxidative stress. Several genes associated with lung metastasis, including ID1, were specifically enriched in EmC. Given the emerging role of OXPHOS in cancer cell survival during dissemination and as established metastases, we propose that the EmC paradigm is a suitable ex vivo model to study signaling pathways relevant for tumor tissue and to assess drug sensitivities and resistance mechanisms of metastatic breast cancer cells ex vivo. SIGNIFICANCEThis study provides an in-depth characterization of a resource-efficient yet powerful 3D culture paradigm to improve the physiological relevance of ex vivo approaches. Applicable to epithelial cancers, this model offers a platform to accelerate the discovery of physiologically relevant signaling pathways and specific cancer cell vulnerabilities.

cancer biology↗

bioRxiv2024

The axillary lymphoid organ - an external, experimentally accessible immune organ in the zebrafish

Lymph nodes and other secondary lymphoid organs play critical roles in immune surveillance and immune activation in mammals, but the deep internal locations of these organs make it challenging to image and study them in living animals. Here, we describe a previously uncharacterized external immune organ in the zebrafish ideally suited for studying immune cell dynamics in vivo, the axillary lymphoid organ (ALO). This small, translucent organ has an outer cortex teeming with immune cells, an inner medulla with a mesh-like network of fibroblastic reticular cells along which immune cells migrate, and a network of lymphatic vessels draining to a large adjacent lymph sac. Noninvasive high-resolution imaging of transgenically marked immune cells can be carried out in the lobes of living animals, and the ALO is readily accessible to external treatment. This newly discovered tissue provides a superb model for dynamic live imaging of immune cells and their interaction with pathogens and surrounding tissues, including blood and lymphatic vessels. TeaserA newly characterized external zebrafish lymphoid organ provides a powerful model for live imaging of immune cell dynamics

developmental biology↗