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Biology subjects

He, J. Y.

Publications and source records attributed to He, J. Y..

3 recordsLinked to original sources

In mouse and gut-on-a-chip models, pre-colonoscopy bowel preparation promotes pathogen colonization of the gut and translocation to other organs

In the United States an estimated 14 million colonoscopies are performed yearly, each requiring patients to undergo bowel preparation, a laxative cleansing of the intestines luminal contents. Despite its widespread use, the effects of bowel preparation on gut physiology and susceptibility to pathogens remains poorly understood, particularly in individuals with compromised gut health. Using mouse and in vitro models, we found that bowel preparation with the laxative polyethylene glycol (PEG) rapidly disrupts, transiently increasing susceptibility to infection by Salmonella Typhimurium, including a non-motile mutant, and by gut pathobionts derived from ulcerative colitis microbiota. Bowel preparation also facilitated bacterial translocation to extraintestinal sites (mesenteric lymph nodes, liver, and spleen) and exacerbated inflammation in a chemically-induced colitis model. Although these findings are preclinical, they suggest that bowel preparation may have underappreciated risks in vulnerable populations, and warrant further clinical investigation.

microbiology↗

Single-cell spatial transcriptomics of fixed, paraffin-embedded biopsies reveals colitis-associated cell networks

Background & AimsImaging-based, single-cell spatial transcriptomics (iSCST) using formalin-fixed, paraffin-embedded (FFPE) tissue could transform translational research by retaining all tissue cell subsets and spatial locations while enabling the analysis of archived specimens. We aimed to develop a robust framework for applying iSCST to archived clinical FFPE mucosal biopsies from patients with inflammatory bowel disease (IBD). MethodsWe performed a comprehensive benchmarking comparison of three iSCST platforms capable of analyzing FFPE specimens. We analyzed FFPE mucosal biopsies (n=57) up to 5 years old from non-IBD controls (HC; n=9) and patients with ulcerative colitis (UC;n=11). After platform-specific cell segmentation, we applied a uniform data processing pipeline to all datasets, including transcript detection, cell annotation, differential gene expression, and neighborhood enrichment. Transcriptomic signatures identified with iSCST were validated using external, publicly available bulk transcriptomic datasets. ResultsA custom 290-plex Xenium gene panel exhibited the highest sensitivity and specificity for transcript detection, enabling precise identification and quantification of diverse cell subsets and differentially expressed genes across cell types and disease states. We mapped transcriptionally distinct fibroblast subsets to discrete spatial locations and identified inflammation-associated fibroblasts (IAFs) and monocytes as a colitis-associated cellular neighborhood. We also identified signatures associated with Vedolizumab (VDZ) responsiveness. VDZ non-responders were characterized by an IAF-monocyte transcriptional signature, while responders exhibited enrichment of epithelial gene sets. ConclusionsOur optimized iSCST framework for archived FFPE biopsies provides unique advantages for assessing the role of colitis-associated cellular networks in routinely collected clinical samples. FFPE-based biomarkers could integrate with existing clinical workflows and potentially aid in risk-stratifying patients.

immunology↗

Perfusable Apparatus For Thick-tissue Creation And Growth (patch) Of Cardiac Tissue

Cardiac tissue engineering has been developed as a potential alternative treatment for heart failure. However, current 3D tissues are limited in size and thickness due to the lack of an effective vascularization method. We have developed a novel bioreactor system to create viable vascularized cardiac tissue from multicellular spheroids using a digital light processing (DLP) 3D bioprinting system. Spheroids were created from induced pluripotent stem cells (iPSC) and cardiac fibroblasts (FB) using special dimple plates for mass production. One centimeter cubic tissues were created from spheroids using a DLP 3D printed mold with vascular channels. The tissue was maintained in a perfusion chamber under regulated flow and pressure following differentiation to cardiac tissue and endothelialization. Mass production of large spheroids (35,000 / tissue, diameter of 395.99 um +/- 101.15 um) was achieved from 170 million iPSCs and 50 million FBs for the creation of 1cm3 cardiac tissue in a 3D printed mold with vascular channels. The cardiac tissues (n=5) were perfused for 20 days under stable pressure of 17.5 +/- 3.05 PSI and flow of 5000 uL/min +/- 1116.42 uL/min. On days 10 and 20, Alamar blue assays showed viability for all five tissues (Alamar blue intensity: Day 10 1.57 +/- 0.15. Day 20 2.21 +/- 0.19). Thick and viable cardiac tissues were created and maintained using a 3D printed vascularized mold and perfusion system for maturation and growth in vitro for 30 days. This technology will open new doors for viable in vitro cardiac tissue creation.

bioengineering↗