25 results on '"Laixin, Xia"'
Search Results
2. The Maternal Microbiome Programs the m6A Epitranscriptome of the Mouse Fetal Brain and Intestine
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Zhuoyu Xiao, Sun Liu, Zengguang Li, Jinru Cui, Hailan Wang, Zihan Wang, Qihuan Ren, Laixin Xia, Zhijian Wang, and Yuan Li
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Cell Biology ,Developmental Biology - Abstract
The microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (m6A) plays important roles in developmental regulation. Although it has been shown that the microbiome affects the mRNA m6A modification of the host, it remains unclear whether the maternal microbiome affects m6A epitranscriptome of the fetus so as to impact fetal development. Here, we found that loss of the maternal microbiome altered the expression of m6A writers and erasers, as well as the m6A methylome of the mouse fetal brain and intestine on embryonic day 18. From the m6A profiles, we identified 2,655 and 2,252 m6A modifications regulated by the maternal microbiome in the fetal brain and intestine, respectively, and we demonstrated that these m6A-modified genes were enriched in the neuro/intestinal developmental pathways, such as the Wnt signaling pathway. Finally, we verified that antibiotic treatment mostly recapitulated changes in m6A, and we further showed that the loss of heterozygosity of Mettl3 rescued m6A levels and the expression changes of some developmental genes in the fetal intestine that resulted from antibiotic treatment. Collectively, our data revealed that the maternal microbiome programs the m6A epitranscriptome of the mouse fetal brain and intestine.
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- 2022
3. Trimethylamine N-Oxide increases soluble fms-like tyrosine Kinase-1 in human placenta via NADPH oxidase dependent ROS accumulation
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Nailiang Zang, Laixin Xia, Ming-xin Yang, Mei Zhong, Qing-xian Chang, Nanbert Zhong, Le-qian Li, Xia Chen, and Qi-tao Huang
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0301 basic medicine ,Placenta ,Trimethylamine N-oxide ,Methylamines ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pre-Eclampsia ,Pregnancy ,Dichlorofluorescein ,Humans ,Secretion ,Cells, Cultured ,Vascular Endothelial Growth Factor Receptor-1 ,030219 obstetrics & reproductive medicine ,NADPH oxidase ,biology ,NADPH Oxidases ,Obstetrics and Gynecology ,Trophoblasts ,Cell biology ,030104 developmental biology ,Gene Expression Regulation ,Reproductive Medicine ,chemistry ,Cell culture ,embryonic structures ,Apocynin ,biology.protein ,Female ,Reactive Oxygen Species ,Oxidation-Reduction ,Tyrosine kinase ,Soluble fms-like tyrosine kinase-1 ,Developmental Biology - Abstract
Backgrounds Preeclampsia (PE) is characterized as placental vascular disturbance and excessive secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) into the maternal circulation. Trimethylamine N-oxide (TMAO, a gut microbe-derived metabolite) is strongly associated with various cardiovascular and cerebrovascular diseases. Recently, we observe that higher maternal circulating TMAO and sFlt-1 in patients with PE. The aims of the present study are to explore the effects of TMAO on placental sFlt-1 production and the underlying mechanism in human placenta. Methods Human placental explants, human placental primary trophoblasts and the extravillous trophoblasts (EVT) cell line (HRT-8/SVneo) were exposured to various concentrations of TMAO (100, 150, 300, and 600 μM). The mRNA expression and protein secretion of sFlt-1 in placental explants, primary trophoblasts and HRT-8/SVneo cells were determined with qPCR and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production in primary trophoblasts and HRT-8/SVneo cells were measured by peroxide-sensitive fluorescent probe dichlorofluorescein diacetate. Results Exposure of placental explants, primary trophoblasts and HRT-8/SVneo cells to TMAO significantly enhanced sFlt-1 at both mRNA and protein levels in a dose dependent manner. Moreover, inhibition of NADPH oxidase with apocynin significantly attenuated TMAO-induced ROS production in primary trophoblasts and HRT-8/SVneo, and suppressed sFlt-1 secretion in placental explants, primary trophoblasts and HRT-8/SVneo. Conclusions Our findings indicated the NADPH oxidase dependent ROS pathway played a critical role in mediating TMAO-induced sFlt-1 generation in human placenta. TMAO may become a potential novel target for pharmacological or dietary interventions to reduce the risk of developing PE.
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- 2021
4. The Maternal Microbiome Programs the m
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Zhuoyu, Xiao, Sun, Liu, Zengguang, Li, Jinru, Cui, Hailan, Wang, Zihan, Wang, Qihuan, Ren, Laixin, Xia, Zhijian, Wang, and Yuan, Li
- Abstract
The microbiome exerts profound effects on fetal development and health, yet the mechanisms underlying remain elusive. N6-methyladenosine (m
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- 2022
5. N6-Methyladenosine co-transcriptionally directs the demethylation of histone H3K9me2
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Rui Xiao, Linjian Xia, Mengtian Yang, Jiaxin Hu, Minchun Li, Xiaona Liu, Mingqiang Deng, Zihan Wang, Laixin Xia, Tianqi Liu, Jinru Cui, Junfang Shi, Xin Cao, Kaifen Tan, Xidong Ye, Shan Xiao, Qizhi Luo, Haoran Zhu, Yuan Li, Zhixiang Zuo, and Sun Liu
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0303 health sciences ,biology ,RNA ,Methylation ,Epigenome ,Chromatin ,Cell biology ,03 medical and health sciences ,0302 clinical medicine ,Histone ,Transcription (biology) ,Gene expression ,Genetics ,biology.protein ,Demethylase ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
A dynamic epigenome is critical for appropriate gene expression in development and health1-5. Central to this is the intricate process of transcription6-11, which integrates cellular signaling with chromatin changes, transcriptional machinery and modifications to messenger RNA, such as N6-methyladenosine (m6A), which is co-transcriptionally incorporated. The integration of these aspects of the dynamic epigenome, however, is not well understood mechanistically. Here we show that the repressive histone mark H3K9me2 is specifically removed by the induction of m6A-modified transcripts. We demonstrate that the methyltransferase METTL3/METTL14 regulates H3K9me2 modification. We observe a genome-wide correlation between m6A and occupancy by the H3K9me2 demethylase KDM3B, and we find that the m6A reader YTHDC1 physically interacts with and recruits KDM3B to m6A-associated chromatin regions, promoting H3K9me2 demethylation and gene expression. This study establishes a direct link between m6A and dynamic chromatin modification and provides mechanistic insight into the co-transcriptional interplay between RNA modifications and histone modifications.
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- 2020
6. Arginine methylation of METTL14 promotes RNA N6-methyladenosine modification and endoderm differentiation of mouse embryonic stem cells
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Jinru Cui, Xueya Zhao, Qizhi Luo, Shan Xiao, Zihan Wang, Wenyi Du, Xiaona Liu, Hailong Wang, Qingwen Wang, Laixin Xia, Dahua Chen, Linjian Xia, Kaifen Tan, Jia Jiang, and Enhui Du
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Epigenomics ,0301 basic medicine ,Protein-Arginine N-Methyltransferases ,Adenosine ,RNA methylation ,Science ,General Physics and Astronomy ,Stem cells ,Arginine ,Methylation ,Article ,General Biochemistry, Genetics and Molecular Biology ,Mice ,03 medical and health sciences ,0302 clinical medicine ,RNA interference ,Gene expression ,Protein methylation ,Animals ,Humans ,RNA, Small Interfering ,Messenger RNA ,Multidisciplinary ,Methyltransferase complex ,Chemistry ,Endoderm ,RNA ,Cell Differentiation ,Mouse Embryonic Stem Cells ,Methyltransferases ,General Chemistry ,RNA modification ,Cell biology ,HEK293 Cells ,030104 developmental biology ,Gene Expression Regulation ,RNA Interference ,Protein Processing, Post-Translational ,030217 neurology & neurosurgery ,HeLa Cells - Abstract
RNA N6-methyladenosine (m6A), the most abundant internal modification of mRNAs, plays key roles in human development and health. Post-translational methylation of proteins is often critical for the dynamic regulation of enzymatic activity. However, the role of methylation of the core methyltransferase METTL3/METTL14 in m6A regulation remains elusive. We find by mass spectrometry that METTL14 arginine 255 (R255) is methylated (R255me). Global mRNA m6A levels are greatly decreased in METTL14 R255K mutant mouse embryonic stem cells (mESCs). We further find that R255me greatly enhances the interaction of METTL3/METTL14 with WTAP and promotes the binding of the complex to substrate RNA. We show that protein arginine N-methyltransferases 1 (PRMT1) interacts with and methylates METTL14 at R255, and consistent with this, loss of PRMT1 reduces mRNA m6A modification globally. Lastly, we find that loss of R255me preferentially affects endoderm differentiation in mESCs. Collectively, our findings show that arginine methylation of METTL14 stabilizes the binding of the m6A methyltransferase complex to its substrate RNA, thereby promoting global m6A modification and mESC endoderm differentiation. This work highlights the crosstalk between protein methylation and RNA methylation in gene expression., The methyltransferase complex of METTL3-METTL14-WTAP is responsible for m6A modification on RNA. Here the authors report that METTL14 arginine 255 (R255) is methylated by PRMT1 and this modification increases interaction of METTL3/METTL14 interaction with WTAP and substrate RNA, promoting m6A methylation activity of the complex.
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- 2021
7. The RNA N6-methyladenosine modification landscape of human fetal tissues
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Shuo Cao, Qi-tao Huang, Yuan Li, Mengtian Yang, Weishi Wang, Junfang Shi, Sun Liu, Shan Xiao, Qizhi Luo, Guiru Jia, Mingqiang Deng, Laixin Xia, Kaifen Tan, Linjian Xia, Xiaona Liu, Chunjiang He, Mei Zhong, and Haoran Zhu
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0303 health sciences ,RNA ,Single-nucleotide polymorphism ,Cell Biology ,Computational biology ,Biology ,Cell biology ,Gene expression profiling ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,030220 oncology & carcinogenesis ,Gene expression ,N6-Methyladenosine ,Enhancer ,Gene ,030304 developmental biology ,Epigenomics - Abstract
A single genome gives rise to diverse tissues through complex epigenomic mechanisms, including N6-methyladenosine (m6A), a widespread RNA modification that is implicated in many biological processes. Here, to explore the global landscape of m6A in human tissues, we generated 21 whole-transcriptome m6A methylomes across major fetal tissues using m6A sequencing. These data reveal dynamic m6A methylation, identify large numbers of tissue differential m6A modifications and indicate that m6A is positively correlated with gene expression homeostasis. We also report m6A methylomes of long intergenic non-coding RNA (lincRNA), finding that enhancer lincRNAs are enriched for m6A. Tissue m6A regions are often enriched for single nucleotide polymorphisms that are associated with the expression of quantitative traits and complex traits including common diseases, which may potentially affect m6A modifications. Finally, we find that m6A modifications preferentially occupy genes with CpG-rich promoters, features of which regulate RNA transcript m6A. Our data indicate that m6A is widely regulated by human genetic variation and promoters, suggesting a broad involvement of m6A in human development and disease.
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- 2019
8. Association between hypertensive disorders of pregnancy and risk of autism in offspring: a systematic review and meta-analysis of observational studies
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Qing-xian Chang, Qi-tao Huang, Jian Zhang, Mei Zhong, Nanbert Zhong, Laixin Xia, Qi-Qiong Wang, Yanhong Yu, and Ruoting Xu
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Gestational hypertension ,medicine.medical_specialty ,Pregnancy ,pre-eclampsia ,Offspring ,business.industry ,hypertensive disorders of pregnancy ,autism ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,Obstetrics and gynaecology ,Autism spectrum disorder ,Family medicine ,mental disorders ,medicine ,Etiology ,Autism ,Medical genetics ,030212 general & internal medicine ,business ,030217 neurology & neurosurgery ,Meta-Analysis ,childhood - Abstract
// Ruo-Ting Xu 1, 2, * , Qing-Xian Chang 3, * , Qi-Qiong Wang 4 , Jian Zhang 5 , Lai-Xin Xia 6 , Nanbert Zhong 3, 7, 8 , Yan-Hong Yu 3 , Mei Zhong 3 and Qi-Tao Huang 3 1 Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China 2 First School of Clinical Medicine, Southern Medical University, Guangzhou, China 3 Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, China 4 Department of Neonatology, Nanfang Hospital, Southern Medical University, Guangzhou, China 5 Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China 6 Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China 7 March of Dimes Global Network for Maternal and Infant Health, White Plains, NY, USA 8 Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA * These authors contributed equally to this work Correspondence to: Qi-Tao Huang, email: 15920454515@163.com Mei Zhong, email: zhongm1960@163.com Keywords: autism; childhood; pre-eclampsia; hypertensive disorders of pregnancy Received: June 05, 2017 Accepted: September 21, 2017 Published: December 07, 2017 ABSTRACT Background: Autism spectrum disorder (ASD) is a common severe pervasive neurodevelopmental disorder of undetermined etiology. Environmental exposures, especially pregnancy complications, have been increasingly recognized as a potential risk factor for ASD. Our aim was to (1) systematically evaluate the association between hypertensive disorders of pregnancy (HDP) and the risk of ASD in offspring, (2) specifically draw a subgroup analysis of disease severity in patients with HDP to achieve more sufficient evidence on this issue. Results: A total of 21 studies were identified with more than 6.5 million participants, including 31,027 ASD probands. A comparative meta-analysis established that offspring born premature to HDP were significantly associated with ASD than matched controls (OR = 1.42, 95% CI: 1.34–1.50). Subgroup analysis of clinical classification include: (1) gestational hypertension, (2) pre-eclampsia, (3) chronic hypertension complicating pregnancy (CHP). The offspring of mothers with pre-eclampsia and CHP have slightly higher risk (OR = 1.43; OR = 1.48, respectively) of ASD than those of mothers with gestational hypertension (OR = 1.37). In consistence with most previous researches, higher ASD prevalence was observed in male than female (OR = 1.38), indicating a potential role for gender in the pathophysiology of ASD. Materials and Methods: We conducted a systematic literature search on PubMed, EMBASE, Web of Science, PsycINFO database and China National Knowledge Infrastructure up to Jun. 2017. Statistical analysis was performed using Stata 10.0. Conclusions: This meta-analysis implies a possible link between HDP and the risk of ASD in offspring. However, further investigation should be conducted to confirm this conclusion, and intensive prenatal surveillance and early prediction for ASD is needed.
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- 2017
9. Gcn5 determines the fate ofDrosophilagermline stem cells through degradation of Cyclin A
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Sun Liu, Tianqi Liu, Wenqing Li, Xiaona Liu, Laixin Xia, Feiyu Mao, Shanshan Yue, Qi Wang, and Shan Xiao
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0301 basic medicine ,Genetics ,fungi ,Cyclin A ,Histone acetyltransferase ,Cell cycle ,Biology ,Biochemistry ,Germline ,Cell biology ,enzymes and coenzymes (carbohydrates) ,03 medical and health sciences ,030104 developmental biology ,Stem cell fate determination ,biology.protein ,Gene silencing ,Stem cell ,Molecular Biology ,Biotechnology ,Cyclin - Abstract
The fluctuating CDK-CYCLIN complex plays a general role in cell-cycle control. Many types of stem cells use unique features of the cell cycle to facilitate asymmetric division. However, the manner in which these features are established remains poorly understood. The cell cycle of Drosophila female germline stem cells (GSCs) is characterized by short G1 and very long G2 phases, making it an excellent model for the study of cell cycle control in stem cell fate determination. Using a Drosophila female GSC model, we found Gcn5, the first discovered histone acetyltransferase, to maintain germline stem cells in Drosophila ovaries. Results showed that Gcn5 is dispensable for the transcriptional silencing of bam, but interacts with Cyclin A to facilitate proper turnover in GSCs. Results also showed that Gcn5 promotes Cyclin A ubiquitination, which is dependent on its acetylating activity. Finally, results showed that knockdown of Cyclin A rescued the GSC-loss phenotype caused by lack of Gcn5. Collectively, these findings support the conclusion that Gcn5 acts through acetylation to facilitate Cyclin A ubiquitination and proper turnover, thereby determining the fate of GSCs.-Liu, T., Wang, Q., Li, W., Mao, F., Yue, S., Liu, S., Liu, X., Xiao, S., Xia, L. Gcn5 determines the fate of Drosophila germline stem cells through degradation of Cyclin A.
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- 2017
10. CVm6A: A Visualization and Exploration Database for m⁶As in Cell Lines
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Yujing, Han, Jing, Feng, Linjian, Xia, Xin, Dong, Xinyang, Zhang, Shihan, Zhang, Yuqi, Miao, Qidi, Xu, Shan, Xiao, Zhixiang, Zuo, Laixin, Xia, and Chunjiang, He
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Internet ,Mice ,User-Computer Interface ,Data Descriptor ,Adenosine ,Databases as Topic ,N6-methyladenosine ,Animals ,Humans ,cell line ,m6A ,visualization - Abstract
N6-methyladenosine (m6A) has been identified in various biological processes and plays important regulatory functions in diverse cells. However, there is still no visualization database for exploring global m6A patterns across cell lines. Here we collected all available MeRIP-Seq and m6A-CLIP-Seq datasets from public databases and identified 340,950 and 179,201 m6A peaks dependent on 23 human and eight mouse cell lines respectively. Those m6A peaks were further classified into mRNA and lncRNA groups. To better understand the potential function of m6A, we then mapped m6A peaks in different subcellular components and gene regions. Among those human m6A modification, 190,050 and 150,900 peaks were identified in cancer and non-cancer cells, respectively. Finally, all results were integrated and imported into a visualized cell-dependent m6A database CVm6A. We believe the specificity of CVm6A could significantly contribute to the research for the function and regulation of cell-dependent m6A modification in disease and development.
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- 2018
11. The RNA N
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Shan, Xiao, Shuo, Cao, Qitao, Huang, Linjian, Xia, Mingqiang, Deng, Mengtian, Yang, Guiru, Jia, Xiaona, Liu, Junfang, Shi, Weishi, Wang, Yuan, Li, Sun, Liu, Haoran, Zhu, Kaifen, Tan, Qizhi, Luo, Mei, Zhong, Chunjiang, He, and Laixin, Xia
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Epigenomics ,Fetal Development ,Adenosine ,Enhancer Elements, Genetic ,Fetus ,Gene Expression Regulation ,Gene Expression Profiling ,Humans ,RNA, Long Noncoding ,Promoter Regions, Genetic ,Transcriptome ,Methylation ,Polymorphism, Single Nucleotide - Abstract
A single genome gives rise to diverse tissues through complex epigenomic mechanisms, including N
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- 2018
12. Heavy Metals Induce Decline of Derivatives of 5-Methycytosine in Both DNA and RNA of Stem Cells
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Shan Xiao, Laixin Xia, Jun Xiong, Bi-Feng Yuan, Qing-Yun Cheng, Yu-Qi Feng, and Xiaona Liu
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0301 basic medicine ,Biology ,Tandem mass spectrometry ,01 natural sciences ,Biochemistry ,Epigenesis, Genetic ,03 medical and health sciences ,chemistry.chemical_compound ,Cytosine ,Mice ,Tandem Mass Spectrometry ,Metals, Heavy ,Animals ,Epigenetics ,Cytotoxicity ,Carcinogen ,Cells, Cultured ,Stem Cells ,010401 analytical chemistry ,RNA ,General Medicine ,DNA ,DNA Methylation ,Molecular biology ,0104 chemical sciences ,030104 developmental biology ,chemistry ,DNA methylation ,5-Methylcytosine ,Molecular Medicine ,Stem cell - Abstract
Toxic heavy metals have been considered to be harmful environmental contaminations. The molecular mechanisms of heavy-metals-induced cytotoxicity and carcinogenicity are still not well elucidated. Previous reports showed exposures to toxic heavy metals can cause a change of DNA cytosine methylation (5-methylcytosine, 5-mC). However, it is still not clear whether heavy metals have effects on the recently identified new epigenetic marks in both DNA and RNA, i.e., 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Here, we established a chemical labeling strategy in combination with liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS) analysis for highly sensitive detection of eight modified cytidines in DNA and RNA. The developed method allowed simultaneous detection of all eight modified cytidines with improved detection sensitivities of 128-443-fold. Using this method, we demonstrated that the levels of 5-hmC, 5-foC, and 5-caC significantly decreased in both the DNA and RNA of mouse embryonic stem (ES) cells while exposed to arsenic (As), cadmium (Cd), chromium (Cr), and antimony (Sb). In addition, we found that treatments by heavy metals induced a decrease of the activities of 10-11 translocation (Tet) proteins. Furthermore, we revealed that a content change of metabolites occurring in the tricarboxylic acid cycle may be responsible for the decline of the derivatives of 5-mC. Our study shed light on the epigenetic effects of heavy metals, especially for the induced decline of the derivatives of 5-mC in both DNA and RNA.
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- 2017
13. Gcn5 determines the fate of
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Tianqi, Liu, Qi, Wang, Wenqing, Li, Feiyu, Mao, Shanshan, Yue, Sun, Liu, Xiaona, Liu, Shan, Xiao, and Laixin, Xia
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Stem Cells ,Cell Cycle ,Ovary ,Cell Differentiation ,Cyclin A ,Drosophila melanogaster ,Germ Cells ,Phenotype ,Animals ,Drosophila Proteins ,Female ,Cell Division ,Histone Acetyltransferases ,Signal Transduction - Abstract
The fluctuating CDK-CYCLIN complex plays a general role in cell-cycle control. Many types of stem cells use unique features of the cell cycle to facilitate asymmetric division. However, the manner in which these features are established remains poorly understood. The cell cycle of
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- 2016
14. Exosome Release Is Regulated by mTORC1
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Xiaoyang Zhao, Qiancheng Song, Jian Yang, Anling Liu, Yue Zhang, Han Zhang, Lei Zheng, Wenchong Zou, Xiaochun Bai, Zhong-Kai Cui, Laixin Xia, Mingqiang Lai, Yu Jiang, Ting Li, Zhe Xing, and Zhipeng Zou
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General Chemical Engineering ,medicine.medical_treatment ,General Physics and Astronomy ,Medicine (miscellaneous) ,exosomes ,02 engineering and technology ,mTORC1 ,010402 general chemistry ,01 natural sciences ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Exosome ,Downregulation and upregulation ,MVBs ,medicine ,General Materials Science ,Messenger RNA ,Full Paper ,rapamycin ,Chemistry ,Growth factor ,Autophagy ,General Engineering ,Full Papers ,021001 nanoscience & nanotechnology ,TSC2 ,Microvesicles ,0104 chemical sciences ,Cell biology ,biological phenomena, cell phenomena, and immunity ,0210 nano-technology ,Intracellular - Abstract
Exosomes are small membrane‐bound vesicles released into extracellular spaces by many types of cells. These nanovesicles carry proteins, mRNA, and miRNA, and are involved in cell waste management and intercellular communication. In the present study, it is shown that exosome release, which leads to net loss of cellular membrane and protein content, is negatively regulated by mechanistic target of rapamycin complex 1 (mTORC1). It is found that in cells and animal models exosome release is inhibited by sustained activation of mTORC1, leading to intracellular accumulation of CD63‐positive exosome precursors. Inhibition of mTORC1 by rapamycin or nutrient and growth factor deprivation stimulates exosome release, which occurs concomitantly with autophagy. The drug‐stimulated release is blocked by siRNA‐mediated downregulation of small GTPase Rab27A. Analysis of the cargo content in exosomes released from rapamycin‐treated cells reveals that inhibition of mTORC1 does not significantly alter its majority protein and miRNA profiles. These observations demonstrate that exosome release, like autophagy, is negatively regulated by mTORC1 in response to changes in nutrient and growth factor conditions.
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- 2018
15. The Niche-Dependent Feedback Loop Generates a BMP Activity Gradient to Determine the Germline Stem Cell Fate
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Guoqiang Zhang, Wenjing Zheng, Laixin Xia, Xiu-Deng Zheng, Dahua Chen, Yi Tao, and Hailong Wang
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endocrine system ,animal structures ,Stromal cell ,Niche ,Cell ,Genes, Insect ,Receptors, Cell Surface ,Protein Serine-Threonine Kinases ,Biology ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Germline ,Animals, Genetically Modified ,Transcription (biology) ,medicine ,Animals ,Drosophila Proteins ,Gene silencing ,Stem Cell Niche ,Ovum ,Feedback, Physiological ,Genetics ,Agricultural and Biological Sciences(all) ,Biochemistry, Genetics and Molecular Biology(all) ,Stem Cells ,Cell biology ,Drosophila melanogaster ,Germ Cells ,medicine.anatomical_structure ,Bone Morphogenetic Proteins ,Mutation ,Female ,Signal transduction ,Stem cell ,General Agricultural and Biological Sciences ,Signal Transduction - Abstract
Summary Stem cells interact with surrounding stromal cells (or niche) via signaling pathways to precisely balance stem cell self-renewal and differentiation [1–4]. However, little is known about how niche signals are transduced dynamically and differentially to stem cells and their intermediate progeny and how the fate switch of stem cell to differentiating cell is initiated. The Drosophila ovarian germline stem cells (GSCs) have provided a heuristic model for studying the stem cell and niche interaction. Previous studies demonstrated that the niche-dependent BMP signaling is essential for GSC self-renewal via silencing bam transcription in GSCs [5–7]. We recently revealed that the Fused (Fu)/Smurf complex degrades the BMP type I receptor Tkv allowing for bam expression in differentiating cystoblasts (CBs) [8]. However, how the Fu is differentially regulated in GSCs and CBs remains unclear. Here we report that a niche-dependent feedback loop involving Tkv and Fu produces a steep gradient of BMP activity and determines GSC fate. Importantly, we show that Fu and graded BMP activity dynamically develop within an intermediate cell, the precursor of CBs, during GSC-to-CB transition. Our mathematic modeling reveals a bistable behavior of the feedback-loop system in controlling the bam transcriptional on/off switch and determining GSC fate.
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- 2012
16. The Fused/Smurf Complex Controls the Fate of Drosophila Germline Stem Cells by Generating a Gradient BMP Response
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Yuanxiang Zhu, Yanjun Mu, Laixin Xia, Dahua Chen, Qinmiao Sun, Anming Meng, Hailong Wang, Shoujun Huang, Shunji Jia, Xiaoming Li, Lijuan Kan, Di Wu, and Wenjing Zheng
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animal structures ,Stromal cell ,Ubiquitin-Protein Ligases ,Protein Serine-Threonine Kinases ,Bone morphogenetic protein ,General Biochemistry, Genetics and Molecular Biology ,Animals ,Drosophila Proteins ,Humans ,Phosphorylation ,Zebrafish ,Hedgehog ,Cells, Cultured ,Genetics ,biology ,Biochemistry, Genetics and Molecular Biology(all) ,Stem Cells ,Ovary ,fungi ,Ubiquitination ,biology.organism_classification ,BMPR2 ,Cell biology ,Ubiquitin ligase ,Drosophila melanogaster ,Germ Cells ,Bone Morphogenetic Proteins ,embryonic structures ,biology.protein ,Female ,Signal transduction ,Stem cell ,Signal Transduction - Abstract
SummaryIn the Drosophila ovary, germline stem cells (GSCs) are maintained primarily by bone morphogenetic protein (BMP) ligands produced by the stromal cells of the niche. This signaling represses GSC differentiation by blocking the transcription of the differentiation factor Bam. Remarkably, bam transcription begins only one cell diameter away from the GSC in the daughter cystoblasts (CBs). How this steep gradient of response to BMP signaling is formed has been unclear. Here, we show that Fused (Fu), a serine/threonine kinase that regulates Hedgehog, functions in concert with the E3 ligase Smurf to regulate ubiquitination and proteolysis of the BMP receptor Thickveins in CBs. This regulation generates a steep gradient of BMP activity between GSCs and CBs, allowing for bam expression on CBs and concomitant differentiation. We observed similar roles for Fu during embryonic development in zebrafish and in human cell culture, implying broad conservation of this mechanism.
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- 2010
17. Otefin, a Nuclear Membrane Protein, Determines the Fate of Germline Stem Cells in Drosophila via Interaction with Smad Complexes
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Dahua Chen, Xiaoyong Jiang, Yingyue Yang, Haidong Huang, Laixin Xia, Lele Yang, Jun Wang, Dongsheng Chen, Lijun Shen, and Qiudong Zhao
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animal structures ,Nuclear Envelope ,Recombinant Fusion Proteins ,SMAD ,Regulatory Sequences, Nucleic Acid ,Biology ,General Biochemistry, Genetics and Molecular Biology ,medicine ,Animals ,Drosophila Proteins ,Gene Silencing ,Nuclear membrane ,Nuclear protein ,BMP signaling pathway ,Molecular Biology ,Cells, Cultured ,Smad4 Protein ,Genetics ,Stem Cells ,Ovary ,Membrane Proteins ,Nuclear Proteins ,Cell Biology ,STEMCELL ,Cell biology ,Chromatin ,Drosophila melanogaster ,Germ Cells ,medicine.anatomical_structure ,Membrane protein ,SIGNALING ,Bone Morphogenetic Proteins ,Mutation ,embryonic structures ,Nuclear lamina ,Female ,RNA Interference ,Signal transduction ,Signal Transduction ,Developmental Biology - Abstract
Nuclear envelope proteins play important roles in chromatin organization, gene regulation, and signal transduction; however, the physiological role of these proteins remains elusive. We found that otefin (ote), which encodes a nuclear lamin-binding protein [corrected], is essential for germline stem cell (GSC) maintenance. We show that Ote, as an intrinsic factor, is both necessary and sufficient to regulate GSC fate. Furthermore, we demonstrate that ote is required for the Dpp/BMP signaling pathway to silence bam transcription. By structure-function analysis, we demonstrate that the nuclear membrane localization of Ote is essential for its role in GSC maintenance. Finally, we show that Ote physically interacts with Medea/Smad4 at the bam silencer element to regulate GSC fate. Thus, we demonstrate that specific nuclear membrane components mediate signal-dependent transcriptional effects to control stem cell behavior.
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- 2008
18. Argonaute 1 regulates the fate of germline stem cells inDrosophila
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Dahua Chen, Ranhui Duan, Abrar Qurashi, Lele Yang, Dongsheng Chen, Laixin Xia, Peng Jin, and Jun Wang
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endocrine system ,Embryo, Nonmammalian ,Subfamily ,Transcription, Genetic ,Piwi-interacting RNA ,Biology ,Germline ,microRNA ,Animals ,Drosophila Proteins ,RasiRNA ,Gene silencing ,Gene Silencing ,Eukaryotic Initiation Factors ,Molecular Biology ,Oligonucleotide Array Sequence Analysis ,Regulation of gene expression ,Genetics ,Stem Cells ,Ovary ,fungi ,DNA Helicases ,Gene Expression Regulation, Developmental ,Argonaute ,MicroRNAs ,Argonaute Proteins ,Drosophila ,Female ,Gene Deletion ,Developmental Biology - Abstract
The Argonaute-family proteins play crucial roles in small-RNA-mediated gene regulation. In Drosophila, previous studies have demonstrated that Piwi, one member of the PIWI subfamily of Argonaute proteins, plays an essential role in regulating the fate of germline stem cells (GSCs). However,whether other Argonaute proteins also play similar roles remains elusive. Here, we show that overexpression of Argonaute 1 (AGO1) protein, another subfamily (AGO) of the Argonaute proteins, leads to GSC overproliferation,whereas loss of Ago1 results in the loss of GSCs. Combined with germline clonal analyses of Ago1, these findings strongly support the argument that Ago1 plays an essential and intrinsic role in the maintenance of GSCs. In contrast to previous observations of Piwi function in the maintenance of GSCs, we show that AGO1 is not required for bag of marbles (bam) silencing and probably acts downstream or parallel of bam in the regulation of GSC fate. Given that AGO1 serves as a key component of the miRNA pathway, we propose that an AGO1-dependent miRNA pathway probably plays an instructive role in repressing GSC/cystoblast differentiation.
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- 2007
19. Construction of a BAC library and identification of Dmrt1 gene of the rice field eel, Monopterus albus
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Fang Zhou, Songhun Jang, Wei Zhao, Hanhua Cheng, Rongjia Zhou, and Laixin Xia
- Subjects
Genetics ,Chromosomes, Artificial, Bacterial ,Bacterial artificial chromosome ,Eels ,Base Sequence ,Contig ,Biophysics ,Intron ,food and beverages ,Cell Biology ,Biology ,Biochemistry ,Genome ,Electrophoresis, Gel, Pulsed-Field ,Exon ,Complementary DNA ,Animals ,Genomic library ,Molecular Biology ,Gene ,Gene Library ,Transcription Factors - Abstract
A bacterial artificial chromosome (BAC) library was constructed using nuclear DNA from the rice field eel (Monopterus albus). The BAC library consists of a total of 33,000 clones with an average insert size of 115 kb. Based on the rice field eel haploid genome size of 600 Mb, the BAC library is estimated to contain approximately 6.3 genome equivalents and represents 99.8% of the genome of the rice field eel. This is first BAC library constructed from this species. To estimate the possibility of isolating a specific clone, high-density colony hybridization-based library screening was performed using Dmrt1 cDNA of the rice field eel as a probe. Both library screening and PCR identification results revealed three positive BAC clones which were overlapped, and formed a contig covering the Dmrt1 gene of 195 kb. By sequence comparisons with the Dmrt1 cDNA and sequencing of first four intron-exon junctions, Dmrt1 gene of the rice field eel was predicted to contain four introns and five exons. The sizes of first and second intron are 1.5 and 2.6 kb, respectively, and the sizes of last two introns were predicted to be about 20 kb. The Dmrt1 gene structure was conserved in evolution. These results also indicate that the BAC library is a useful resource for BAC contig construction and molecular isolation of functional genes.
- Published
- 2006
20. Alternative splicing and differential expression of P450c17 (CYP17) in gonads during sex transformation in the rice field eel
- Author
-
Hanhua Cheng, Yiqing Guo, Laixin Xia, Rongjia Zhou, and Hongshi Yu
- Subjects
Male ,endocrine system ,Sex Differentiation ,Gonad ,Molecular Sequence Data ,Biophysics ,Biology ,Biochemistry ,medicine ,Animals ,Humans ,Protein Isoforms ,Hermaphroditic Organisms ,Amino Acid Sequence ,Northern blot ,Gonads ,Molecular Biology ,Gene ,In Situ Hybridization ,Phylogeny ,Regulation of gene expression ,Genetics ,Eels ,Sexual differentiation ,Ovotestis ,Alternative splicing ,Steroid 17-alpha-Hydroxylase ,Cell Biology ,Sex Determination Processes ,Sex reversal ,Alternative Splicing ,medicine.anatomical_structure ,Gene Expression Regulation ,Female ,Sequence Alignment - Abstract
Several mechanisms were used in determination of the development of the male or female of vertebrates. The genes for determination of sequential hermaphrodite sex are unknown. Here, we reported cloning, alternative splicing, and expression patterns of the CYP17 gene of the rice field eel, a teleost fish with a characteristic of nature sex reversal. The CYP17 gene of the rice field eel was clustered into the CYP17 gene group of all the other vertebrates, especially into the fish subgroup. Four isoforms of the CYP17 were generated in gonads by alternative splicing and polyadenylation. Alternative splicing events of all these isoforms occurred in 3(') regions, which encoded three different sizes (517, 512, and 159aa) of proteins. RT-PCR results indicate specific expression in gonads of these isoforms. Northern blot analysis shows that expression patterns of the CYP17 (dominantly expressed in testis, less in ovary, and the least in ovotestis) are consistent with the sex reversal process of the rice field eel. In situ hybridization further shows its specific expression in germinal lamellae, the gonadal epithelium of the gonads. These findings indicate that CYP17 is differentially regulated in a sex- and developmentally specific manner, suggesting that the CYP17 potentially has important roles in gonad differentiation during sex reversal of the rice field eel.
- Published
- 2003
21. Molecular cloning and expression of Sox17 in gonads during sex reversal in the rice field eel, a teleost fish with a characteristic of natural sex transformation
- Author
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Hanhua Cheng, Yiqing Guo, Rui Wang, Xiao Huang, Rongjia Zhou, and Laixin Xia
- Subjects
Male ,endocrine system ,animal structures ,HMG-box ,Cloning, Organism ,Molecular Sequence Data ,Biophysics ,Biology ,Polymerase Chain Reaction ,Biochemistry ,Mice ,Gene expression ,SOXF Transcription Factors ,Animals ,Humans ,Hermaphroditic Organisms ,Amino Acid Sequence ,Molecular Biology ,Gene ,Phylogeny ,DNA Primers ,Genetics ,Eels ,Sexual differentiation ,Base Sequence ,Sequence Homology, Amino Acid ,Ovotestis ,High Mobility Group Proteins ,Proteins ,Chromosome ,Cell Biology ,Sex Determination Processes ,Sex reversal ,DNA-Binding Proteins ,Testis determining factor ,embryonic structures ,Female ,Sequence Alignment ,Transcription Factors - Abstract
The Sox is a large family of genes which encode transcription factors with high-mobility-group DNA binding domain related to the SRY, with diverse roles in development, and a few of them are involved in sex determination and differentiation. We report here the identification of Sox17 gene of the rice field eel, a teleost fish with a characteristic of natural sex transformation. This gene, located on chromosome 5, consists of two exons which encode a 399-amino acid protein with a conserved HMG box. Phylogenetic analysis shows that the rice field eel Sox17 fits within the Sox17 clade of vertebrates. The rice field eel Sox17 was dominantly expressed in gonads of male, female, and intersex, besides in brain and spleen. Gene expression analysis by in situ hybridization showed its expression in testis, ovary, and ovotestis, and specifically in the gonadal lamellae of ovary, ovotestis, and testis and developing spermatogenic cells of testis, suggesting that they have potentially important roles in gonadal differentiation during sex reversal in this species.
- Published
- 2003
22. A small natural molecule promotes mitochondrial fusion through inhibition of the deubiquitinase USP30
- Author
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Xiaohui Wang, Jinhua Liu, Haijing Jin, Lei Liu, Du Feng, Lei Du, Yueying Wang, Laixin Xia, Chaojun Yan, Hai-Yang Liu, Ming Chen, Ziheng Chen, Wen Yue, Jun Wang, Xiao-Jiang Hao, Chen Yan, Quan Chen, Zhiyin Song, Xiaohu Huang, and Hao Wu
- Subjects
MFN2 ,Mitochondrial Dynamics ,Mitochondrial Membrane Transport Proteins ,Oxidative Phosphorylation ,GTP Phosphohydrolases ,Mitochondrial Proteins ,Mitochondrial membrane transport protein ,Gene Knockout Techniques ,Mice ,MFN1 ,Animals ,Humans ,Enzyme Inhibitors ,Molecular Biology ,Cells, Cultured ,Mitochondrial DNA inheritance ,biology ,Cell Biology ,Research Highlight ,Cell biology ,Mitochondria ,mitochondrial fusion ,DNAJA3 ,biology.protein ,Original Article ,Mitochondrial fission ,ATP–ADP translocase ,Thiolester Hydrolases ,Ubiquitin-Specific Proteases ,Diterpenes ,HeLa Cells - Abstract
Mitochondrial fusion is a highly coordinated process that mixes and unifies the mitochondrial compartment for normal mitochondrial functions and mitochondrial DNA inheritance. Dysregulated mitochondrial fusion causes mitochondrial fragmentation, abnormal mitochondrial physiology and inheritance, and has been causally linked with a number of neuronal diseases. Here, we identified a diterpenoid derivative 15-oxospiramilactone (S3) that potently induced mitochondrial fusion to restore the mitochondrial network and oxidative respiration in cells that are deficient in either Mfn1 or Mfn2. A mitochondria-localized deubiquitinase USP30 is a target of S3. The inhibition of USP30 by S3 leads to an increase of non-degradative ubiquitination of Mfn1/2, which enhances Mfn1 and Mfn2 activity and promotes mitochondrial fusion. Thus, through the use of an inhibitor of USP30, our study uncovers an unconventional function of non-degradative ubiquitination of Mfns in promoting mitochondrial fusion.
- Published
- 2013
23. Quantity versus quality: the sperm war
- Author
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Shan Xiao and Laixin Xia
- Subjects
Invited Research Highlight ,endocrine system ,biology ,urogenital system ,Urology ,media_common.quotation_subject ,General Medicine ,lcsh:Diseases of the genitourinary system. Urology ,lcsh:RC870-923 ,biology.organism_classification ,Sperm ,Female sperm storage ,Evolutionary biology ,Sexual selection ,Quality (business) ,Mating ,Drosophila ,reproductive and urinary physiology ,Sperm motility ,media_common - Abstract
The evolution of sperm traits manifests itself prolifically across species, and postcopulatory sexual selection (PSS), as executed by the female, accompanies this process. The adaptive significance of some sperm traits (for example, the shape and number of sperms) is well understood. However, the evolution of germ size has not been fully exploited. The most recent study by Lüpold et al.1 reveals that the evolution of longer sperm is driven by the female seminal receptacle and mating frequency in Drosophila, which, in turn, increases the benefits to females. These findings provide a comprehensive interpretation regarding the evolution of sperm size.
- Published
- 2016
24. Effete-mediated degradation of Cyclin A is essential for the maintenance of germline stem cells in Drosophila
- Author
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Dongsheng Chen, Xiaoyong Jiang, Qinmiao Sun, Qi Wang, Lijuan Kan, Dahua Chen, Laixin Xia, and Haidong Huang
- Subjects
Cyclin D ,Cyclin A ,Mitosis ,Germline ,Anaphase-Promoting Complex-Cyclosome ,parasitic diseases ,Animals ,Drosophila Proteins ,Molecular Biology ,Cells, Cultured ,Cyclin ,biology ,Hydrolysis ,Stem Cells ,fungi ,Ovary ,Ubiquitination ,Ubiquitin-Protein Ligase Complexes ,Ubiquitin ligase ,Cell biology ,Mutation ,Ubiquitin-Conjugating Enzymes ,biology.protein ,Drosophila ,Female ,Stem cell ,Drosophila Protein ,Cyclin A2 ,Developmental Biology ,Protein Binding - Abstract
Increasing evidence supports the idea that the regulation of stem cells requires both extrinsic and intrinsic mechanisms. However, much less is known about how intrinsic signals regulate the fate of stem cells. Studies on germline stem cells (GSCs) in the Drosophila ovary have provided novel insights into the regulatory mechanisms of stem cell maintenance. In this study, we demonstrate that a ubiquitin-dependent pathway mediated by the Drosophila eff gene, which encodes the E2 ubiquitin-conjugating enzyme Effete (Eff), plays an essential role in GSC maintenance. We show that Eff both physically and genetically interacts with dAPC2, a key component of the anaphase-promoting complex (APC), which acts as a multisubunit E3 ligase and plays an essential role in targeting mitotic regulators for degradation during exit from mitosis. This interaction indicates that Eff regulates the APC/C-mediated proteolysis pathway in GSCs. Moreover, we show that expression of a stable form of Cyclin A, but not full-length Cyclin A, results in GSC loss. Finally we show that, in common with APC2, Eff is required for the ubiquitylation of Cyclin A, and overexpression of full-length Cyclin A accelerates the loss of GSCs in the eff mutant background. Collectively, our data support the idea that Effete/APC-mediated degradation of Cyclin A is essential for the maintenance of germline stem cells in Drosophila. Given that the regulation of mitotic Cyclins is evolutionarily conserved between flies and mammals, our study also implies that a similar mechanism may be conserved in mammals.
- Published
- 2009
25. Molecular cloning and expression of the osteoclast-stimulating-factor-like gene from the rice field eel
- Author
-
Hanhua Cheng, Rongjia Zhou, Yiqing Guo, Laixin Xia, and Hongshi Yu
- Subjects
endocrine system ,DNA, Complementary ,Molecular Sequence Data ,Biology ,Homology (biology) ,Hermaphrodite ,Gene expression ,Animals ,Amino Acid Sequence ,Gonads ,Gene ,In Situ Hybridization ,Phylogeny ,DNA Primers ,Genetics ,Expressed Sequence Tags ,Expressed sequence tag ,Sexual differentiation ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,Gene Expression Profiling ,Intracellular Signaling Peptides and Proteins ,General Medicine ,Sequence Analysis, DNA ,Blotting, Northern ,Smegmamorpha ,Gene expression profiling ,Blotting, Southern ,Testis determining factor ,Animal Science and Zoology ,Peptides ,Sequence Alignment - Abstract
Sexual development in vertebrates is a complex process. Vertebrates use several mechanisms to determine the development of a male or female organism. The genes for determination of sequential hermaphrodite sex are unknown. We identified a homologue of human osteoclast-stimulating factor (OSF) in the rice field eel, a teleost that undergoes natural sex transformation from female, via intersex, to male during its lifetime. The rice field eel OSF-like gene cDNA encoded a peptide of 214 amino acids that contains a c-Src homology 3 domain, proline-rich region, and ankyrin repeats, suggesting potential involvement in cell signaling. The gene was clustered into the OSF gene group of all the other vertebrates. Although expressed in the three kinds of gonads and in other tissues, OSF-like gene expression in gonads of all the three sexes was restricted to the gonadal germinal epithelium, from where bipotential gonia (oogonia or spermatogonia) will differentiate, suggesting that the OSF-like gene may be involved in sexual differentiation, in addition to its other roles as a regulator in development.
- Published
- 2004
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