Exosomes facilitate cell-to-cell communication and are involved in key biological processes. Understanding the mechanisms regulating exosome production could offer new therapeutic insights for various diseases. Here, Prof. Zhong’s team demonstrates that exosome secretion is significantly inhibited when glucose is replaced with galactose as the primary carbon source in the culture medium. This glycometabolic regulation of exosome secretion is dependent on the cellular hexosamine biosynthetic pathway (HBP). Inhibition of HBP via gene knockdown, pharmacological blockade, or metabolite deprivation markedly suppresses exosome secretion. Mechanistically, HBP regulates multivesicular body (MVB) outward trafficking and its fusion with the plasma membrane via synaptosomal-associated protein 25 (SNAP25). O-GlcNAcylation of SNAP25 promotes soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly, thereby facilitating exosome release. In summary, these findings reveal a critical role of HBP and protein O-GlcNAcylation in exosome secretion, which may provide new therapeutic targets for exosome-associated diseases, including cancer and inflammatory disorders.

Hair loss and graying, the earliest visible hallmarks of skin aging, result from the functional decline of hair follicle stem cells (HFSCs) and their niche. Dr. Zhao and colleagues conducted a comprehensive analysis of human scalp samples using single-cell RNA sequencing (11 samples, 57,181 cells in total) and spatial transcriptomics (1 sample) to detail the mechanisms involved. The study confirmed the transitional stages of three mitotic keratinocyte subtypes. Comparison of middle-aged and young scalps revealed three key age-associated changes: activated AP-1 transcription factor complex in keratinocytes; up-regulated DCT gene in melanocytes; and a dramatic decrease in BMP and non-canonical WNT (ncWNT) signaling within the critical dermal papilla-keratinocyte crosstalk. This breakdown of essential inter-cellular communication and activation of stress signals provides valuable, cell-resolved insights into hair follicle aging, supporting the development of future regenerative therapies targeting these pathways.

The fungal species Candida auris is spreading across the globe, and gaining in virulence - but there are strategies available and underway to combat the invasive and drug resistant germ, according to a new review by a Hackensack Meridian Center for Discovery and Innovation (CDI) scientist and colleagues. 

A new ‘biomimetic’ model of brain circuits and function at multiple scales produced naturalistic dynamics and learning, and even identified curious behavior by some neurons that had gone unnoticed in real-brain data

Understanding how cells decide their fate is a central challenge in biology, complicated by the fact that single-cell RNA sequencing captures only static snapshots of highly complex and dynamic changes in cell state. In a recent study, researchers from Japan developed a computational method, called ddHodge, that can accurately reconstruct cell state dynamics, shedding light on how genes drive cell fate decisions. Their technique could be useful in developmental biology, regenerative medicine, and cancer research.

Intestinal Stem Cells (ISCs) derived from a patient's own cells have garnered significant attention as a new alternative for treating intractable intestinal diseases due to their low risk of rejection. However, clinical application has been limited by safety and regulatory issues arising from conventional culture methods that rely on animal-derived components (xenogeneic components). A KAIST research team has developed an advanced culture technology that stably grows ISCs without animal components while simultaneously enhancing their migration to damaged tissues and regenerative capabilities.