Biology subjects

Ju, S.

Publications and source records attributed to Ju, S..

24 records · Page 2Linked to original sources

bioRxiv2020

Naa12 rescues embryonic lethality in Naa10-Deficient Mice in the amino-terminal acetylation pathway

Amino-terminal acetylation is catalyzed by a set of N-terminal acetyltransferases (NATs). The NatA complex (including X-linked Naa10 and Naa15) is the major acetyltransferase, with 40-50% of all mammalian proteins being potential substrates. However, the overall role of amino-terminal acetylation on a whole-organism level is poorly understood, particularly in mammals. Male mice lacking Naa10 show no globally apparent in vivo amino-terminal acetylation impairment and do not exhibit complete embryonic lethality. Rather Naa10 nulls display increased neonatal lethality, and the majority of surviving undersized mutants exhibit a combination of hydrocephaly, cardiac defects, homeotic anterior transformation, piebaldism and urogenital anomalies. Naa12 is a previously unannotated Naa10-like paralogue with NAT activity that genetically compensates for Naa10. Mice deficient for Naa12 have no apparent phenotype, whereas mice deficient for Naa10 and Naa12 display embryonic lethality. The discovery of Naa12 adds to the currently known machinery involved in amino-terminal acetylation in mice.

developmental biology↗

bioRxiv2020

Defining the ultrastructure of the hematopoietic stem cell niche by correlative light and electron microscopy

The blood system is supported by hematopoietic stem and progenitor cells (HSPCs) found in a specialized microenvironment called the niche. Many different niche cell types support HSPCs, however how they interact and their ultrastructure has been difficult to define. Here we show that single endogenous HSPCs can be tracked by light microscopy, then identified by serial block-face scanning electron microscopy (SBEM) at multiscale levels. Using the zebrafish larval kidney marrow (KM) niche as a model, we followed single fluorescently-labeled HSPCs by light sheet microscopy, then confirmed their exact location in a 3D SBEM dataset. Our approach allowed us to identify dopamine beta-hydroxylase (dbh) positive ganglia cells as a previously uncharacterized functional cell type in the HSPC niche. By integrating multiple imaging modalities, we could resolve the ultrastructure of single rare cells deep in live tissue and define all contacts between an HSPC and its surrounding niche cell types.

developmental biology↗

bioRxiv2020

Mitochondria surveillance systems trigger innate immune responses to bacterial pathogens via AMPK pathway in C. elegans

Pathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reported C. elegans can monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.

immunology↗

bioRxiv2020

SynGAP splice isoforms differentially regulate synaptic plasticity and dendritic development

SynGAP is a synaptic Ras GTPase-activating protein (GAP) with four C-terminal splice variants: 1, 2, {beta}, and {gamma}. Although recent studies have implicated SYNGAP1 haploinsufficiency in ID/ASD pathogenesis, the degree to which each SynGAP isoform contributes to disease pathogenesis remains elusive. Here we demonstrate that individual SynGAP isoforms exhibit unique spatiotemporal expression and have distinct roles in neuronal and synaptic development. The SynGAP-1 isoform, which undergoes robust liquid-liquid phase-separation with PSD-95 and is highly-enriched in synapses, is expressed late in development and disperses from synaptic spines in response to LTP-inducing synaptic activity to allow for AMPA receptor insertion and spine enlargement. In contrast, the SynGAP-{beta} isoform, which undergoes less liquid-liquid phase-separation with PSD95 and is less synaptically targeted, is expressed early in development and promotes dendritic arborization. Interestingly, a SynGAP-1 mutation that disrupts phase separation and synaptic targeting abolishes its function in plasticity and instead drives dendritic arbor development like the {beta} isoform. These results demonstrate that distinct phase separation and synaptic targeting properties of SynGAP isoforms determine their function. HighlightsO_LISynGAP-1, 2, {beta}, {gamma} isoforms have distinct spatiotemporal expression and function in the brain. C_LIO_LISynGAP-1 is required for plasticity, while {beta} is required for dendritic development. C_LIO_LILiquid-liquid phase separation of SynGAP-1 is required for its role in plasticity. C_LIO_LISynGAP isoforms may differentially contribute to SYNGAP1 related human NDDs. C_LI

neuroscience↗

bioRxiv2019

Meiosis related cancer-testis genes correlate with tumor aneuploidy and immune infiltration in 21 cancer types

The meiosis stage of spermatogenesis and the aneuploidy generation in tumorigenesis are highly linked. Cancer-testis genes (CT genes) were specifically expressed in testis and cancers and may serve as the molecular basis of the shared features between spermatogenesis and tumorigenesis. In the present study, we integrated multi-omics data from bulk samples and cell lines, and single cell RNA-Seq data from testis and two tumors to systematically investigate the association between CT genes and aneuploidy. After ranking genes according to their association with aneuploidy level, we found that CT genes, especially CT genes specifically expressed in meiosis, showed a consistently positive correlation with aneuploidy and homologous recombination deficiency (HRD) level. Similar results were also found in the CT non-coding genes. Then, we constructed a regulatory network based on the single cell RNA-seq data and revealed that the gain of accelerator transcriptional factors (TFs) E2F7 and E2F8 and the loss of the stabilizer TFs RFX2 and NFYA aberrantly activated CT genes in the cancers and were associated with the increase of HRD level. Finally, we found that the association between CT genes and cytotoxic infiltrating lymphocytes can be influenced by the HRD level. In sum, our results revealed the evidence of pseudomeiotic functions of CT genes in the aneuploidy generation process in the cancer cells. The results may help illuminate the origin of aneuploidy in cancers and guide future immunotherapy targeting CT antigens.

genomics↗

bioRxiv2019

Ibuprofen-mediated potential inhibition of biofilm development and quorum sensing in Pseudomonas aeruginosa

Pseudomonas aeruginosa is one of the leading causes of opportunistic and hospital-acquired infections worldwide. The infection with P. aeruginosa is frequently linked with clinical treatment difficulties given drug resistance and abuse of antibiotics. Ibuprofen, a widely used non-steroidal anti-inflammatory drug, has been previously reported to exert antimicrobial activity, although the specific mechanism of its action requires additional investigation. Given the regulation effects on quorum sensing (QS), we hypothesized that inhibition of P. aeruginosa with ibuprofen is linked with the QS systems. First, we assessed the action of ibuprofen in P. aeruginosa by measuring CFU. The antimicrobial activity of ibuprofen was evaluated by crystal violent staining and acridine orange staining at various drug concentrations (0, 50, 75, and 100 g/mL). Moreover, the effect of ibuprofen on different QS virulence factors, such as pyocyanin, elastase, protease, and rhamnolipids, was assessed revealing a concentration-dependent decrease (P<0.05). The effect of ibuprofen was confirmed by liquid chromatography/mass spectrometry analysis of 3-oxo-C12-HSL and C4-HSL production. In addition, qRT-PCR results identified significant suppression of Las and Rhl gene expression after 18 hours of treatment with ibuprofen (P<0.05), with the most significant suppression observed at the concentration of 75 g/mL. Functional complementation with exogenous 3-oxo-C12-HSL and C4-HSL suggested that C4-HSL can recover the production of virulence factors and biofilm formation in P. aeruginosa. Molecular docking of ibuprofen with QS-associated proteins revealed high binding affinity. In summary, the results suggest that ibuprofen is a candidate drug for the treatment of clinical infections with P. aeruginosa.

microbiology↗