Biology subjects

Hu, J. K.

Publications and source records attributed to Hu, J. K..

3 recordsLinked to original sources

bioRxiv2026

Cell jamming transition is regulated by mitochondrial pyruvate transport and endocytosis

Epithelial tissues undergo dynamic transitions between fluid-like collective motion and mechanically jammed states during development, injury repair, and disease progression. However, the cellular programs that drive these transitions and regulate collective behavior remain unclear. Using a controlled crowding model integrated with live-cell imaging and time-resolved multi-omics, we demonstrate that epithelial crowding triggers early metabolic changes characterized by increased mitochondrial pyruvate anaplerosis that precedes the jamming transition. Functional inhibition of mitochondrial pyruvate import is sufficient to sustain collective cell motility, impeding jamming transition in crowded cells. This unjammed state is driven by enhanced cytoskeletal remodeling and requires RhoA-myosin II activity. Mechanistically, we show that elevated cytoskeletal signaling promotes macropinocytic uptake, which serves as a required feedback loop to maintain motility. These findings identify mitochondrial pyruvate utilization as a key regulator that links metabolic remodeling to the endocytic control of epithelial fluidity.

cell biology↗

bioRxiv2024

Whole Tissue Imaging of Cellular Boundaries at Sub-Micron Resolutions for Automatic Cell Segmentation: Applications in Epithelial Bending of Ectodermal Appendages

For decades, biologists have relied on confocal microscopy to understand cellular morphology and fine details of tissue structure. However, traditional confocal microscopy of tissues faces limited light penetration, typically less than 100 {micro}m, due to tissue opacity. To address this challenge, researchers have developed tissue clearing protocols compatible with confocal microscopy. Unfortunately, these protocols often struggle to retain cell boundary markers, especially at high resolutions necessary for precise cell segmentation. In this work, we introduce a method that preserves cell boundary markers and matches the refractive index of tissues with water. This technique enables the use of high-magnification, long working distance water-dipping objectives. The sub-micron resolutions achieved with this approach allows us to automatically segment each individual cell using a trained neural network segmentation model. These segmented images facilitate the quantification of cell properties and morphology of the entire three-dimensional tissue. As a demonstration of this methodology, we first examine mandibles of transgenic mice that express fluorescent proteins in their cell membranes. We then extend this technique to a non-model animal, the catshark, investigating the cellular properties of its dental lamina and dermal denticles - invaginating and evaginating ectodermal structures, respectively. Our technique thus provides a powerful tool to quantify in high throughput the 3D structures of cells and tissues during organ morphogenesis.

developmental biology↗

bioRxiv2022

Understanding the development of oral epithelial organs through single cell transcriptomic analysis

During vertebrate craniofacial development, the oral epithelium begins as a simple and morphologically homogeneous tissue. It then gives rise to locally complex structures, including the developing teeth, salivary glands, and taste buds. While there is significant knowledge about the molecular mechanisms regulating the morphogenesis of these organs at later stages, how the epithelium is initially patterned and specified to generate diverse cell types and organs remains largely unknown. To elucidate the genetic programs that direct the formation of distinct oral epithelial populations, we mapped the transcriptional landscape of embryonic day (E) 12 mouse mandibular epithelia at single cell resolution. Our analysis identified key transcription factors and gene regulatory networks that define different epithelial cell types as well as regions patterned along the oral-aboral axis. By examining the spatiotemporal expression of region-specific markers in embryonic mandibles, our results pointed to a model where the dental field is progressively confined to its position by the formation of the aboral epithelium anteriorly and the non-dental oral epithelium posteriorly. Using our data, we also identified Ntrk2 as a promoter of cell proliferation in the forming incisor, contributing to its invagination. Together, our results provide a detailed transcriptional atlas of the developing mandibular epithelium and unveil new genetic markers and regulators that are present during the specification of various oral epithelial structures.

developmental biology↗