Biology subjects

Wang, C.-M.

Publications and source records attributed to Wang, C.-M..

5 recordsLinked to original sources

bioRxiv2024

Human Mesofluidic Intestinal Model for Studying Transport of Drug Carriers and Bacteria Through a Live Mucosal Barrier

The intestinal mucosal barrier forms a critical interface between lumen contents such as bacteria, drugs, and drug carriers and the underlying tissue. Current in vitro intestinal models, while recapitulating certain aspects of this barrier, generally present challenges with respect to imaging transport across mucus and uptake into enterocytes. A human mesofluidic small intestinal chip was designed to enable facile visualization of a mucosal interface created by growing primary human intestinal cells on a vertical hydrogel wall separating channels representing the intestinal lumen and circulatory flow. Type I collagen, fortified via cross-linking to prevent deformation and leaking during culture, was identified as a suitable gel wall material for supporting primary organoid-derived human duodenal epithelial cell attachment and monolayer formation. Addition of DAPT and PGE2 to culture medium paired with air-liquid interface culture increased the thickness of the mucus layer on epithelium grown within the device for 5 days from approximately 5 mm to 50 m, making the model suitable for revealing intriguing features of interactions between luminal contents and the mucus barrier using live cell imaging. Time-lapse imaging of nanoparticle diffusion within mucus revealed a zone adjacent to the epithelium largely devoid of nanoparticles up to 4.5 hr after introduction to the lumen channel, as well as pockets of dimly lectin-stained mucus within which particles freely diffused, and apparent clumping of particles by mucus components. Multiple particle tracking conducted on the intact mucus layer in the chip revealed significant size-dependent differences in measured diffusion coefficients. E. coli introduced to the lumen channel were freely mobile within the mucus layer and appeared to intermittently contact the epithelial surface over 30 minute periods of culture. Mucus shedding into the lumen and turnover of mucus components within cells were visualized. Taken together, this system represents a powerful tool for visualization of interactions between luminal contents and an intact live mucosal barrier.

bioengineering↗

bioRxiv2024

A Strategic Blend of Stabilizing Polymers to Control Particle Surface Charge for Enhanced Mucus Transport and Cell Binding

Mucus layers, viscoelastic gels abundant in anionic mucin glycoproteins, obstruct therapeutic delivery across all mucosal surfaces. We found that strongly positively charged nanoparticles (NPs) rapidly adsorb a mucin protein corona in mucus, impeding cell binding and uptake. To overcome this, we developed mucus-evading, cell-adhesive (MECS) NPs with variable surface charge using Flash NanoPrecipitation, by blending a neutral poly(ethylene glycol) (PEG) corona for mucus transport with a small amount, 5 wt%, of polycationic dimethylaminoethyl methacrylate (PDMAEMA) for increased cell targeting. In vitro experiments confirmed rapid mucus penetration and binding to epithelial cells by MECS NPs, suggesting a breakthrough in mucosal drug delivery.

biophysics↗

bioRxiv2022

Amis Pacilo and Yami Cipoho are not the same as the Pacific breadfruit starch crop--Target enrichment phylogenomics of a long-misidentified Artocarpus species sheds light on the northward Austronesian migration from the Philippines to Taiwan

Breadfruit is a common tree species in Taiwan. In the indigenous Austronesian Amis culture of eastern Taiwan, breadfruit is known as Pacilo, and its fruits are consumed as food. On Lanyu (Botel Tobago) where the indigenous Yami people live, breadfruit is called Cipoho and used for constructing houses and plank-boats. Elsewhere in Taiwan, breadfruit is also a common ornamental tree. As an essential component of traditional Yami culture, Cipoho has long been assumed to have been transported from the Batanes Island of the Philippines to Lanyu. As such, it represents a commensal species that potentially can be used to test the hypothesis of the northward Austronesian migration into Taiwan. However, recent phylogenomic studies using target enrichment show that Taiwanese breadfruit might not be the same as the Pacific breadfruit (Artocarpus altilis) that was domesticated in Oceania and widely cultivated throughout the tropics. To resolve persistent misidentification of this culturally and economically important tree species of Taiwan, we sampled 36 trees of Taiwanese Artocarpus and used the Moraceae probe set to enrich 529 nuclear genes. Along with 28 archived Artocarpus sequence datasets (representing a dozen taxa from all subgenera), phylogenomic analyses showed that all Taiwanese breadfruit samples, together with a cultivated ornamental tree from Hawaii, form a fully supported clade within the A. treculianus complex, which is composed only of endemic Philippine species. Morphologically, the Taiwanese breadfruit matches the characters of A. treculianus. Within the Taiwanese samples of A. treculianus, Amis samples form a fully supported clade derived from within the paraphyletic grade composed of Yami samples, suggesting a Lanyu origin. Results of our target enrichment phylogenomics are consistent with the scenario that Cipoho was transported northward from the Philippines to Lanyu by Yami ancestors, though the possibility that A. treculianus is native to Lanyu cannot be ruled out completely.

plant biology↗

bioRxiv2021

Endometrial Gap Junction Expression - Early Indicators of Endometriosis and Integral to Invasiveness

Endometriosis is an invasive disease, and a leading cause of pain, infertility and disability among women, with an incidence 10 fold that of cancer. A more complete understanding of disease pathogenesis is essential for the development of non-surgical diagnostic assays and non-hormonal therapeutics. Avoidance of immune clearance and implantation of endometrial tissue on peritoneal surfaces are features of endometriosis lesion formation that overlap with cancer metastasis. Connexins, and the gap junctions they form, have been implicated in cancer progression, and may be associated endometriosis pathophysiology. Single cell transcriptomic profiling of endometrial epithelial and stromal cells from women with endometriosis reveals a striking and progressive shift in expression of connexins and related regulatory and junctional genes. We demonstrate that gap junction coupling between endometrial cells and the peritoneal mesothelium is dramatically induced, specifically in endometriosis patients, and is required for invasion by inducing breakdown of the mesothelial barrier function.

cell biology↗

bioRxiv2020

Single-cell chromatin profiling reveals demethylation-dependent metabolic vulnerabilities of breast cancer epigenome

Metabolic reprogramming in cancer cells not only sustains bioenergetic and biosynthetic needs but also influences transcriptional programs, yet how chromatin regulatory networks are rewired by altered metabolism remains elusive. Here we investigate genome-scale chromatin remodeling in response to 2-hydroxyglutarate (2HG) oncometabolite using single-cell assay for transposase accessible chromatin with sequencing (scATAC-seq). We find that 2HG enantiomers differentially disrupt exquisite control of epigenome integrity by limiting -ketoglutarate (KG)-dependent DNA and histone demethylation, while enhanced cell-to-cell variability in the chromatin regulatory landscape is most evident upon exposure to L2HG enantiomer. Despite the highly heterogeneous responses, 2HG largely recapitulates two prominent hallmarks of the breast cancer epigenome, i.e., global loss of 5-hydroxymethylcytosine (5hmC) and promoter hypermethylation, particularly at tumor suppressor genes involved in DNA damage repair and checkpoint control. Single-cell mass cytometry further demonstrates downregulation of BRCA1, MSH2 and MLH1 in 2HG-responsive subpopulations, along with acute reversal of chromatin remodeling upon withdrawal. Collectively, this study provides a molecular basis for metabolism-epigenome coupling and identifies metabolic vulnerabilities imposed on the breast cancer epigenome.

cancer biology↗