Wulftange, W. J. | Search bioRxiv

bioRxiv2023

Enteric glial hub cells coordinate intestinal motility

The enteric nervous system is a complex network of neurons and glia within the gut that coordinate gut motility. By optimizing single nucleus RNA-sequencing methods and spatial transcriptomics, we generated maps of the mouse duodenum and identified distinct molecular classes of enteric glia across the intestine with unique morphological and spatial identities. Here we show enteric glial functional specialization, with one myenteric subtype directly sensing force and expressing the mechanosensory ion channel PIEZO2. Genetic reduction of PIEZO2 in enteric glial populations enriched for this mechanosensory subtype led to defects in gastrointestinal motility. These results provide insight into the multifaceted functions of distinct enteric glial cell subtypes in maintaining gut health, and emphasize the importance of considering subtype-specific roles of enteric glia in a wide range of diseases and disorders.

neuroscience↗

bioRxiv2017

Tissue architectural cues drive the emergence of non-random trafficking of human tumor cells in the larval zebrafish

Sites of metastasis are non-random, with certain types of cancers showing organ preference during distal colonization. Using multiple brain- and bone marrow-seeking human and murine breast cancer subclones, we determined that tumor cells that home to specific murine organs (brain and bone marrow) ultimately colonized analogous tissues (brain and caudal vein plexus [CVP]) in larval zebrafish. We then exploited the zebrafish model to delineate factors leading to differential cell homing and extravasation. Bone marrow-tropic clones showed higher expression of integrins and focal adhesions associated with mechanosensing machinery than brain-tropic clones and were more sensitive to vessel topography during extravasation. Knockdown of {beta}1 integrin reduced extravasation and redistributed organ targeting from disordered vessels in the CVP to the brain. Our results show that organ selectivity is driven by topography- and cell type-dependent extravasation at the tumor-endothelial interface in the larval zebrafish and provide important insights into the early stages of metastasis.

biophysics↗