Biology subjects

Chan, S. C.

Publications and source records attributed to Chan, S. C..

5 recordsLinked to original sources

bioRxiv2026

Hepatocyte nuclear factor-1β recruits the nucleosome remodeling and deacetylase complex to activate gene transcription

Mutations affecting the transcription factor hepatocyte nuclear factor-1{beta} (HNF-1{beta}) are the most common monogenic cause of congenital anomalies of the kidney and urinary tract. The mechanism whereby HNF-1{beta} regulates gene transcription remains unclear. Here, we performed an unbiased proteomic screen and found that endogenous HNF-1{beta} interacts with core subunits of the nucleosome remodeling and deacetylase complex (NuRD) in renal epithelial cells. Genome-wide ChIP-seq studies demonstrated colocalization of endogenous HNF-1{beta} and the core NuRD subunits GATAD2A, CHD4, and MBD3 at 2,776 primarily intergenic and intronic sites in native chromatin from wild-type renal epithelial cells. NuRD co-occupancy at 628 of the sites (22.6%) was reduced in the absence of HNF-1{beta}. Of the 628 HNF-1{beta}-dependent NuRD-occupied sites, 113 sites (18.2%) showed higher ATAC-seq peaks, indicative of open chromatin, and enrichment of histone H3 lysine-27 (H3K27) acetylation, indicative of active enhancers, in wild-type cells compared to HNF-1{beta}-deficient cells. Correlation with transcriptomic profiles in wild-type and HNF-1{beta}-deficient cells revealed that most of the sites were located near genes that are activated by HNF-1{beta}. Knockdown of CHD4 with shRNA resulted in decreased expression of 67 HNF-1{beta}-regulated genes that contained nearby NuRD and HNF-1{beta} co-occupied sites. Collectively, these results demonstrate that HNF-1{beta} recruits the NuRD complex resulting in H3K27 acetylation and chromatin opening and leading to gene activation. Our findings reveal a new mechanism of HNF-1{beta}-dependent gene expression and expand the role of the NuRD complex in gene activation at distal enhancers.

biochemistry↗

bioRxiv2025

Age-related inflammatory changes and perineuronal net dynamics: implications for neurodegenerative disorders.

BackgroundHealthy aging alone can lead to cognitive decline, decreased brain size, protein aggregation, accumulation of senescent cells and neuroinflammation. Furthermore, age is the primary risk factor for several neurodegenerative disorders such as Parkinsons and Alzheimers disease. Age-related neuroinflammation, as known as inflammaging, is thought to restrict brain plasticity. Perineuronal nets (PNNs), specialized extracellular matrix structures surrounding fast-spiking parvalbumin (PV) interneurons, regulate plasticity and protect neurons from oxidative stress. Given the known impact of inflammaging on neural circuits, this study examines age-associated changes in PNN homeostasis, glial activation, and neuroinflammation in two brain regions relevant to age-related neurodegenerative diseases. MethodsWe analyzed young (4-month-old) and aged (22-month-old) C57BL/6J male mice for several behavioral phenotypes [hippocampal-dependent spatial learning using the Barnes maze; locomotion and anxiety-related behaviors using Open field and T-maze]. Using immunostaining, PNNs (Wisteria floribunda agglutinin and aggrecan), PV interneurons, and microglial activation (Iba1) were quantified in both the hippocampus and dorsal striatum. Glial morphology was examined using a battery of cell body, branching, and endpoint analyses. Quantitative RT-PCR was used to analyze changes in the gene expression of inflammatory and extracellular matrix markers. ResultsAged mice exhibited hippocampal-dependent memory deficits without alterations in locomotion or anxiety-related behavior. PNN counts increased in the aged hippocampus, particularly in CA2, with a higher proportion of WFA+ and aggrecan+ PNNs. In contrast, PNN homeostasis was maintained in the dorsal striatum. In general, Aged mice showed increases in microglial activation and a subset of inflammatory markers. We report brain region- and age-specific gene expression changes in complement, matrix metalloproteinases, and other inflammatory markers. Aged striatal microglia displayed an activated morphology with larger cell bodies and reduced branching, as well as increased expression of markers for microgliosis (Iba1, TREM2, CD68). ConclusionsThese findings suggest that aging differentially affects neuroinflammation and PNN integrity across brain regions. The hippocampus exhibits PNN accumulation, neuroinflammation, and behavioral changes, whereas the striatum maintains PNN homeostasis concurrent with increased microglial activation. This work suggests that neuroinflammation contributes to age-related changes in PNNs and behavior underscoring the importance of region-specific therapeutic strategies targeting PNN regulation.

neuroscience↗

bioRxiv2020

Analysis of PPI networks of transcriptomic expression identifies hub genes Associated with Newcastle disease virus persistent infection in bladder cancer

MotivationBladder cancer cells acquire persistent infection associated with oncolytic Newcastle disease virus (NDV) in which its molecular events are still unclear. This poses a potential problem for oncolytic virus application for cancer therapy. To unravel the molecular mechanism underlying the development of NDV persistent infection in bladder cancer, we used mRNA expression profile of the persistently infected bladder cancer cells to construct PPI network. ResultsBased on path and module exploring in the PPI network, the bridges were found mainly from pathways of p53 signalling, ECM-receptor interaction, and TGF-beta signalling by the upregulated mRNAs, to the antigen processing and presentation, protein processing in endoplasmic reticulum, completement and coagulation cascades by the downregulated mRNAs in NDV persistent TCCSUPPi cells. In persistent EJ28Pi cells comparatively, connections were identified mainly from pathways of renal carcinoma, viral carcinogenesis, Ras signalling and cell cycle by the upregulated mRNAs, to the Wnt signalling, HTLV-I infection and pathways in cancer by the downregulated mRNAs. This connection was mainly dependent on of RPL8- HSPA1A/HSPA4 in TCCSUPPi cells and EP300, PTPN11, RAC1 - TP53, SP1, CCND1 and XPO1 in EJ28Pi cells. Oncomine validation showed that the top hub genes identified in the network that includes RPL8, THBS1, F2 from TCCSUPPi and TP53 and RAC1 from EJ28Pi are involved in the development and progression of bladder cancer. Protein-drug interaction network, have identified several drugs targets that could be used to disconnect the linkages between modules and prevent bladder cancer cells from acquiring NDV persistent infection. This is the first time reporting the PPI network analysis of differentially expressed mRNAs of the NDV persistently infected bladder cancer cell lines which provide an insight into screening drugs that could be used together with NDV to manage bladder cancer resistance to therapy and progression.

bioinformatics↗

bioRxiv2020

Functional Transcriptome Analysis of Bladder Cancer Cell Lines Persistently Infected with Oncolytic Newcastle Disease Virus

BackgroundNewcastle disease virus (NDV) has been an attractive virotherapy agent that targets various type of human cancers while leaving normal cells unharmed. Wild-type NDV strain AF2240 has been found to persistently infect subpopulation of cancer cells in vitro, making the cells less susceptible to NDV-mediated oncolysis. It is proposed that transcriptome profiling of NDV persistently infected bladder cancer cell lines will provide insights to understand such occurrence by identifying specific pathways associated with NDV persistent infection due to transcriptomic dysregulation. ResultsTranscriptome profiling revealed a total of 63 and 134 differentially expressed genes (DEGs) from NDV persistently infected TCCSUPPi and EJ28Pi bladder cancer cells relative to their uninfected controls, respectively. Of the 63 DEGs identified for TCCSUPPi cells, 25 DEGs were upregulated (log2 fold-change [≥] 0) and 38 DEGs were downregulated (log2 fold-change [≤] 0). These genes were significantly enriched in the molecular function of calcium binding (GO:0005509) and DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227) and the enriched important upregulated pathways were mainly heme metabolism, TGF-beta signaling and spermatogenesis. As for EJ28Pi, 55 DEGs were upregulated (log2 fold-change [≥] 0) and 79 DEGs were downregulated (log2 fold-change [≤] 0). These DEGs resulted in significantly enriched molecular function such as protein domain specific binding (GO:0019904) and RNA polymerase II regulatory region sequence-specific DNA binding (GO:0000977). The enriched important upregulated pathways were allograft rejection, KRAS signaling up and interferon gamma response. Other important pathways that were downregulated in both the NDV-persistently infected cell lines were angiogenesis, apoptosis, and xenobiotic metabolism. ConclusionThe transcriptome profiles (RNA-Seq) of these cell lines suggest that evasion of apoptosis and increase in TGF-beta signaling and interferon gamma response activities are crucial for establishment of NDV persistent infection in bladder cancer cells. Findings from this study provide the molecular basis that warrant further study on how bladder cancer cells acquired NDV persistent infection. Resolving the mechanism of persistent infection will facilitate the application of NDV for more effective treatment of bladder cancer.

cancer biology↗

bioRxiv2017

Long-range infra-sound acoustic signaling inhuman in vivo

Acupuncture is widely deployed today, but its basic physiology with Qi and meridian is not understood. This letter postulates that Qi is an infrasound wave packet and meridian is the muscle waveguide. Using video cameras and signal processing in an IRB approved clinical experiment we performed a comparison between control and electro-activated statistical tests on the long range (50-80cm) unidirectional transmission of Qi (p = 0.025). In the reverse direction, there is no transmission even in a distance of less than 10 cm (p = 0.545). The rectification is a surprise but in full agreement with Huang Di Nei Jing.

physiology↗