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Biology subjects

Mou, C.

Publications and source records attributed to Mou, C..

5 recordsLinked to original sources

Characterizing the metabolomes of microglia, astrocytes, and neurons in aging and Alzheimer's brains

Neurons and glia are distinct in their morphology, development, and function, possessing unique transcriptomes and proteomes, but little is known about their metabolomes. The challenge of brain cell metabolic profiling is to obtain a large number of cells for reliable analysis. Here, we purified microglia, astrocytes, and neurons from mouse brains, identifying >70 metabolites through targeted metabolomics and 9,854 metabolite features via untargeted metabolomics. We systematically characterized cell type-enriched metabolites and metabolic pathways, revealing an enrichment of glutathione (GSH) and polyamine metabolism in microglia. This enrichment was validated in vivo and showed significant decreases with aging and in an Alzheimers disease (AD) model. Notably, GSH and polyamine metabolism correlated strongly with chemokine-related gene expression. Disrupting the GSH pathway in microglia resulted in downregulation of chemokine-related genes, aberrant morphogenesis, and {beta}-amyloid deposition. Our results provide a valuable resource (https://metabolismocean.org/braincell) for metabolic studies related to aging, AD, and other neurological diseases.

neuroscience↗

Hypoxia impacts small intestinal organoid stemness and differentiation

Comprised of several cell types functioning differently, the small intestinal epithelial cells perform their functions and synergistically maintain homeostasis in the first part of the mammalian intestine. Due to the uneven distribution of the vessel, the oxygen level exhibits a gradient decreasing pattern in the normal intestine and becomes aberrant in some intestinal diseases. In this work, we find certain levels of hypoxia simulated by cobaltous chloride (CoCl2) caused an increase in the secretive cell types and a decrease in the absorptive cell types in vitro cultured mouse small intestinal organoids. Importantly, the intestinal stem cell amount is impacted which leads to attenuated epithelial regeneration. Our study highlights the cell-type-specific alterations under the hypoxia insult, which gives possible therapeutic hints for hypoxia-relevant gastrointestinal diseases.

cancer biology↗

BREVIPEDICELLUS and ERECTA mediate expression of AtPRX17 in preventing Arabidopsis callus retardation and browning

Efficient in vitro callus generation is fundamental to tissue culture propagation, a process required for plant regeneration and transgenic breeding for desired phenotypes. Identifying genes and regulatory elements that prevent callus retardation and browning is essential to facilitate the development of vitro callus systems. Here we show that BREVIPEDICELLUS (BP) and ERECTA (ER) pathways in Arabidopsis callus are converged to prevent callus browning and positively regulate an isoperoxidase gene AtPRX17 expression in the rapid growth callus. Loss of functions in both BP and ER resulted in markedly increasing callus browning. Transgenic lines with pro35S::AtPRX17 in the bp-5 er105 double mutant background fully rescued this phenotypic abnormality. Using plant in vitro DNA-binding assays, we observed that BP protein bound directly to the upstream sequence of AtPRX17 to promote its transcription during callus growth. ER is a universally presenting factor required for cell proliferation and growth, we show that ER positively regulates expression of a transcription factor WRKY6, which also directly binds to an additional site of the AtPRX17 promoter for its high expression. Our data reveals an important molecular mechanism in regulating expression of peroxidase isozyme to reduce Arabidopsis callus browning. HighlightBREVIPEDICELLUS and ERECTA are involved in regulating Arabidopsis callus browning by controlling expression of AtPRX17.

plant biology↗

Tuning electrical stimulation of the cervical vagus nerve for abdominal signaling while reducing cardiovascular side effects

Electrical vagus nerve stimulation (VNS) has the potential to treat a wide variety of diseases by modulating afferent and efferent communication to the heart, lungs, esophagus, stomach, and intestines. Although distal vagal nerve branches, close to end organs, could provide a selective therapeutic approach, these locations are often surgically inaccessible. In contrast, the cervical vagus nerve has been targeted for decades using surgically implantable cuff electrodes to treat epileptic seizures and depression; however, to date, clinical implementation of VNS has relied on an electrode with contacts that fully wrap around the nerve, producing non-selective activation of the entire nerve. Here we demonstrate selective cervical VNS using cuff electrodes with multiple contacts around the nerve circumference to target different functional pathways. These flexible probes were adjusted to the diameter of the nerve using an adhesive hydrogel wrap to create a robust electrode interface. Our approach was verified in a rat model by demonstrating that cervical VNS produces neural activity in the abdominal vagus nerve while limiting effects on the cardiovascular system (i.e., changes in heart rate or blood pressure). This study demonstrates the potential for selective cervical VNS as a therapeutic approach for modulating distal nerve branches while reducing off target effects. This methodology could potentially be refined to treat gastrointestinal, metabolic, inflammatory, cardiovascular, and respiratory diseases amenable to vagal neuromodulatory control.

neuroscience↗

OsLUGL involved in floral development through regulating auxin level and OsARFs expression in rice (Oryza sative L.)

Specification of floral organ identity is critical for floral morphology and inflorescence architecture. Floral organ identity in plants is controlled by floral homeotic A/B/C/D/E-class genes. Although multiple genes regulate floral organogenesis our understanding of the regulatory network remains fragmentary. Here, we characterized rice floral organ gene KAIKOUXIAO (KKX), mutation of which produces an uncharacteristic open hull, abnormal seed, and semi-sterility. KKX encodes a putative LEUNIG-like (LUGL) transcriptional co-repressor. OsLUGL is preferentially expressed in young panicles and its protein can interact with OsSEU, which functions were reported as an adaptor for LEUNIG. OsLUGL-OsSEU functions together as a transcriptional regulatory complex to control organ identity specification through regulation of MADS-box genes. During this process, SEP3 (such as OsMADS8) and AP1 (such as OsMADS18) serve as the DNA-binding partner of OsLUGL-OsSEU complex. Further studies indicated that OsMADS8 and OsMADS18 could bind the promoter of OsGH3-8 and regulate its expression. The altered expression of OsGH3-8 caused the increased auxin level and the decreased expression of OsARFs. Overall, our results demonstrate a possible pathway whereby OsLUGL-OsSEU-OsAP1-OsSEP3 complex as a transcriptional regulator by targeting the promoter of OsGH3-8 directly, affecting auxin level, OsARFs expression level and thereby influencing floral development. These findings provide a valuable insight into the molecular functions of OsLUGL in rice floral development. HighlightOsLUGL through forming OsLUGL-OsSEU-OsAP1-OsSEP3 complex regulate OsGH3-8 expression, and regulate auxin level and OsARFs expression indirectly. This work is a new insight to floral development molecular mechanism.

genetics↗