532 results on '"Fan, Guoping"'
Search Results
2. Distinct patterns of responses in endothelial cells and smooth muscle cells following vascular injury
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Ding, Xili, An, Qin, Zhao, Weikang, Song, Yang, Tang, Xiaokai, Wang, Jing, Chang, Chih-Chiang, Zhao, Gexin, Hsiai, Tzung, Fan, Guoping, Fan, Yubo, and Li, Song
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Biomedical and Clinical Sciences ,Atherosclerosis ,2.1 Biological and endogenous factors ,Aetiology ,Cardiovascular ,Mice ,Humans ,Animals ,Endothelial Cells ,Vascular System Injuries ,Muscle ,Smooth ,Vascular ,Vascular Cell Adhesion Molecule-1 ,Ligands ,Mice ,Knockout ,ApoE ,Myocytes ,Smooth Muscle ,Apolipoproteins E ,Heat-Shock Proteins ,Cardiovascular disease ,Vascular Biology ,Biomedical and clinical sciences ,Health sciences - Abstract
Vascular smooth muscle cells (SMCs) are heterogeneous, and their differential responses to vascular injury are not well understood. To address this question, we performed single-cell analysis of vascular cells to a ligation injury in mouse carotid arteries after 3 days. While endothelial cells had a homogeneous activation of mesenchymal genes, less than 30% of SMCs responded to the injury and generated 2 distinct clusters - i.e., proinflammatory SMCs and stress-responsive SMCs. Proinflammatory SMCs were enriched with high levels of inflammatory markers such as vascular cell adhesion molecule-1 while stress-responsive SMCs overexpressed heat shock proteins. Trajectory analysis suggested that proinflammatory SMCs were potentially derived from a specific subpopulation of SMCs. Ligand-receptor pair analysis showed that the interaction between macrophages and proinflammatory SMCs was the major cell-cell communication among all cell types in the injured arteries. In vitro coculture demonstrated that VCAM1+ SMCs had a stronger chemotactic effect on macrophage recruitment than VCAM1- SMCs. Consistently, the number of VCAM1+ SMCs significantly increased in injured arteries and atherosclerotic lesions of ApoE-/- mice and human arteries. These findings provide insights at the single-cell level on the distinct patterns of endothelial cells and SMC responses to vascular injury.
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- 2022
3. Comparison of retinal degeneration treatment with four types of different mesenchymal stem cells, human induced pluripotent stem cells and RPE cells in a rat retinal degeneration model
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Liu, Qian, Liu, Jun, Guo, Minmei, Sung, Tzu-Cheng, Wang, Ting, Yu, Tao, Tian, Zeyu, Fan, Guoping, Wu, Wencan, and Higuchi, Akon
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- 2023
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4. Brain methylome remodeling selectively regulates neuronal activity genes linking to emotional behaviors in mice exposed to maternal immune activation
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Ma, Li, Wang, Feng, Li, Yangping, Wang, Jing, Chang, Qing, Du, Yuanning, Sadan, Jotham, Zhao, Zhen, Fan, Guoping, Yao, Bing, and Chen, Jian-Fu
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- 2023
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5. Chemical-induced phase transition and global conformational reorganization of chromatin
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Wang, Tengfei, Shi, Shuxiang, Shi, Yuanyuan, Jiang, Peipei, Hu, Ganlu, Ye, Qinying, Shi, Zhan, Yu, Kexin, Wang, Chenguang, Fan, Guoping, Zhao, Suwen, Ma, Hanhui, Chang, Alex C. Y., Li, Zhi, Bian, Qian, and Lin, Chao-Po
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- 2023
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6. Global Transcriptional and Epigenetic Reconfiguration during Chemical Reprogramming of Human Retinal Pigment Epithelial Cells into Photoreceptor-like Cells
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Deng, Xiaoqian, Lee, Ryan, Lim, Sin Yee, Zhong, Zheng, Wang, Jing, Liu, Yizhi, and Fan, Guoping
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Biomedical and Clinical Sciences ,Ophthalmology and Optometry ,Eye Disease and Disorders of Vision ,Stem Cell Research - Nonembryonic - Human ,Stem Cell Research - Induced Pluripotent Stem Cell ,Stem Cell Research ,Neurosciences ,Genetics ,Human Genome ,Underpinning research ,Aetiology ,Development of treatments and therapeutic interventions ,5.2 Cellular and gene therapies ,2.1 Biological and endogenous factors ,1.1 Normal biological development and functioning ,Generic health relevance ,Eye ,Epigenesis ,Genetic ,Epithelial Cells ,Humans ,Retina ,Retinal Degeneration ,Retinal Pigment Epithelium ,Retinal Pigments ,human retinal pigment epithelial cells ,photoreceptor-like cells ,chemical reprogramming ,single-cell RNA sequencing ,DNA methylation sequencing ,Biological sciences ,Biomedical and clinical sciences - Abstract
Retinal degenerative diseases are frequently caused by the loss of retinal neural cells such as photoreceptors. Cell replacement is regarded as one of the most promising therapies. Multiple types of stem and somatic cells have been tested for photoreceptor conversion. However, current induction efficiencies are still low and the molecular mechanisms underlying reprogramming remain to be clarified. In this work, by combining treatment with small molecules, we directly reprogrammed human fetal retinal pigment epithelial (RPE) cells into chemically induced photoreceptor-like cells (CiPCs) in vitro. Bulk and single-cell RNA sequencing, as well as methylation sequencing, were performed to understand the transcriptional and epigenetic changes during CiPCs conversion. A multi-omics analysis showed that the direct reprogramming process partly resembled events of early retina development. We also found that the efficiency of CiPCs conversion from RPE is much better than that from human dermal fibroblasts (HDF). The small molecules effectively induced RPE cells into CiPCs via suppression of the epithelial-to-mesenchymal transition (EMT). Among the signaling pathways involved in CiPCs conversion, glutamate receptor activation is prominent. In summary, RPE cells can be efficiently reprogrammed into photoreceptor-like cells through defined pharmacological modulations, providing a useful cell source for photoreceptor generation in cell replacement therapy for retinal degenerative diseases.
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- 2022
7. Reversing neural circuit and behavior deficit in mice exposed to maternal inflammation by Zika virus
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Ma, Li, Wang, Jing, Ge, Jianlong, Wang, Yuan, Zhang, Wei, Du, Yuanning, Luo, Jun, Li, Yangping, Wang, Feng, Fan, Guoping, Chen, Rong, Yao, Bing, Zhao, Zhen, Guo, Ming‐Lei, Kim, Woong‐Ki, Chai, Yang, and Chen, Jian‐Fu
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Behavioral and Social Science ,Mental Health ,Pediatric ,Neurosciences ,Basic Behavioral and Social Science ,Brain Disorders ,Aetiology ,2.1 Biological and endogenous factors ,Mental health ,Neurological ,Reproductive health and childbirth ,Good Health and Well Being ,Animals ,Female ,Hippocampus ,Inflammation ,Mice ,Prefrontal Cortex ,Pregnancy ,Zika Virus ,Zika Virus Infection ,chemogenetics ,mouse behaviors ,neural circuit ,Zika virus ,Biochemistry and Cell Biology ,Developmental Biology - Abstract
Zika virus (ZIKV) infection during pregnancy is linked to various developmental brain disorders. Infants who are asymptomatic at birth might have postnatal neurocognitive complications. However, animal models recapitulating these neurocognitive phenotypes are lacking, and the circuit mechanism underlying behavioral abnormalities is unknown. Here, we show that ZIKV infection during mouse pregnancy induces maternal immune activation (MIA) and leads to autistic-like behaviors including repetitive self-grooming and impaired social memory in offspring. In the medial prefrontal cortex (mPFC), ZIKV-affected offspring mice exhibit excitation and inhibition imbalance and increased cortical activity. This could be explained by dysregulation of inhibitory neurons and synapses, and elevated neural activity input from mPFC-projecting ventral hippocampus (vHIP) neurons. We find structure alterations in the synaptic connections and pattern of vHIP innervation of mPFC neurons, leading to hyperconnectivity of the vHIP-mPFC pathway. Decreasing the activity of mPFC-projecting vHIP neurons with a chemogenetic strategy rescues social memory deficits in ZIKV offspring mice. Our studies reveal a hyperconnectivity of vHIP to mPFC projection driving social memory deficits in mice exposed to maternal inflammation by ZIKV.
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- 2021
8. Asymmetric Cell Division of Fibroblasts is An Early Deterministic Step to Generate Elite Cells during Cell Reprogramming
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Song, Yang, Soto, Jennifer, Wang, Pingping, An, Qin, Zhang, Xuexiang, Hong, SoonGweon, Lee, Luke P, Fan, Guoping, Yang, Li, and Li, Song
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Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Genetics ,1.1 Normal biological development and functioning ,Underpinning research ,Animals ,Asymmetric Cell Division ,Cellular Reprogramming ,Fibroblasts ,Mice ,Mice ,Inbred C57BL ,Models ,Animal ,asymmetric cell division ,cell fate determination ,direct reprogramming ,epigenetic state - Abstract
Cell reprogramming is considered a stochastic process, and it is not clear which cells are prone to be reprogrammed and whether a deterministic step exists. Here, asymmetric cell division (ACD) at the early stage of induced neuronal (iN) reprogramming is shown to play a deterministic role in generating elite cells for reprogramming. Within one day, fibroblasts underwent ACD, with one daughter cell being converted into an iN precursor and the other one remaining as a fibroblast. Inhibition of ACD significantly inhibited iN conversion. Moreover, the daughter cells showed asymmetric DNA segregation and histone marks during cytokinesis, and the cells inheriting newly replicated DNA strands during ACD became iN precursors. These results unravel a deterministic step at the early phase of cell reprogramming and demonstrate a novel role of ACD in cell phenotype change. This work also supports a novel hypothesis that daughter cells with newly replicated DNA strands are elite cells for reprogramming, which remains to be tested in various reprogramming processes.
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- 2021
9. Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations
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He, Di, Wang, Di, Lu, Ping, Yang, Nan, Xue, Zhigang, Zhu, Xianmin, Zhang, Peng, and Fan, Guoping
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Biological Sciences ,Bioinformatics and Computational Biology ,Biomedical and Clinical Sciences ,Immunology ,Oncology and Carcinogenesis ,Clinical Research ,Lung Cancer ,Cancer ,Rare Diseases ,Genetics ,Lung ,2.1 Biological and endogenous factors ,Aetiology ,Inflammatory and immune system ,Adenocarcinoma of Lung ,Aged ,Biomarkers ,Tumor ,Dendritic Cells ,ErbB Receptors ,Female ,Gene Expression Regulation ,Neoplastic ,Humans ,Lung Neoplasms ,Lymphocytes ,Tumor-Infiltrating ,Male ,Middle Aged ,Mutation ,Myeloid Cells ,Prognosis ,Sequence Analysis ,RNA ,Single-Cell Analysis ,Tumor Microenvironment ,Clinical Sciences ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Lung adenocarcinoma (LUAD) harboring EGFR mutations prevails in Asian population. However, the inter-patient and intra-tumor heterogeneity has not been addressed at single-cell resolution. Here we performed single-cell RNA sequencing (scRNA-seq) of total 125,674 cells from seven stage-I/II LUAD samples harboring EGFR mutations and five tumor-adjacent lung tissues. We identified diverse cell types within the tumor microenvironment (TME) in which myeloid cells and T cells were the most abundant stromal cell types in tumors and adjacent lung tissues. Within tumors, accompanied by an increase in CD1C+ dendritic cells, the tumor-associated macrophages (TAMs) showed pro-tumoral functions without signature gene expression of defined M1 or M2 polarization. Tumor-infiltrating T cells mainly displayed exhausted and regulatory T-cell features. The adenocarcinoma cells can be categorized into different subtypes based on their gene expression signatures in distinct pathways such as hypoxia, glycolysis, cell metabolism, translation initiation, cell cycle, and antigen presentation. By performing pseudotime trajectory, we found that ELF3 was among the most upregulated genes in more advanced tumor cells. In response to secretion of inflammatory cytokines (e.g., IL1B) from immune infiltrates, ELF3 in tumor cells was upregulated to trigger the activation of PI3K/Akt/NF-κB pathway and elevated expression of proliferation and anti-apoptosis genes such as BCL2L1 and CCND1. Taken together, our study revealed substantial heterogeneity within early-stage LUAD harboring EGFR mutations, implicating complex interactions among tumor cells, stromal cells and immune infiltrates in the TME.
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- 2021
10. Culture conditions of mouse ESCs impact the tumor appearance in vivo
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Tian, Chenglei, Wang, Jing, Ye, Xiaoying, Chen, Jiyu, Zheng, Rongyan, Yu, Hanwen, Li, Jie, Yin, Guoxing, Liu, Linlin, Zhao, Nannan, Feng, Guofeng, Zhu, Zhengmao, Wang, Jichang, Fan, Guoping, and Liu, Lin
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- 2023
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11. Asc-2P Sustains Mitochondrial Glycolysis and Promotes Neural Progenitor Cell Activation via Metabotropic Glutamate Receptor 7
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Zhao, Jian, primary, Wang, Ying, additional, Fang, Jing, additional, Hu, Ganlu, additional, Tang, Kailin, additional, Zeng, Xianglu, additional, Wang, Changzheng, additional, Yu, Yongcun, additional, Zeng, Tao, additional, Cao, Zhiwei, additional, and Fan, Guoping, additional
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- 2024
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12. Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis
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Mao, Xiying, An, Qin, Xi, Huiyu, Yang, Xian-Jie, Zhang, Xiangmei, Yuan, Songtao, Wang, Jinmei, Hu, Youjin, Liu, Qinghuai, and Fan, Guoping
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Biological Sciences ,Bioinformatics and Computational Biology ,Regenerative Medicine ,Stem Cell Research - Nonembryonic - Non-Human ,Stem Cell Research - Embryonic - Human ,Biotechnology ,Eye Disease and Disorders of Vision ,Genetics ,Stem Cell Research ,Neurosciences ,Underpinning research ,1.1 Normal biological development and functioning ,Eye ,Biomarkers ,Fluorescent Antibody Technique ,Gene Expression Profiling ,Gene Expression Regulation ,Developmental ,Gene Regulatory Networks ,High-Throughput Nucleotide Sequencing ,Human Embryonic Stem Cells ,Humans ,Immunophenotyping ,Organogenesis ,Organoids ,Retina ,Single-Cell Analysis ,Tissue Culture Techniques ,commitment ,early human retinal development ,human embryonic stem cell ,retina ,retinal progenitor ,single-cell RNA-seq ,Biochemistry and Cell Biology ,Clinical Sciences ,Biochemistry and cell biology - Abstract
The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans.
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- 2019
13. The size of cell-free mitochondrial DNA in blood is inversely correlated with tumor burden in cancer patients
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An, Qin, Hu, Youjin, Li, Qingjiao, Chen, Xufeng, Huang, Jiaoti, Pellegrini, Matteo, Zhou, Xianghong Jasmine, Rettig, Matthew, and Fan, Guoping
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Biological Sciences ,Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Urologic Diseases ,Prostate Cancer ,Human Genome ,Genetics ,2.1 Biological and endogenous factors ,Aetiology ,circulating cell-free DNA ,tumor burden ,cancer progression ,liquid biopsy - Abstract
Circulating cell-free DNAs (cfDNAs) are fragmented DNA molecules released into the blood by cells. Previous studies have suggested that mitochondria-originated cfDNA fragments (mt-cfDNAs) in cancer patients are more fragmented than those from healthy controls. However, it is still unknown where these short mt-cfDNAs originate, and whether the length of mt-cfDNAs can be correlated with tumor burden and cancer progression. In this study, we first performed whole-genome sequencing analysis (WGS) of cfDNAs from a human tumor cell line-xenotransplantation mouse model and found that mt-cfDNAs released from transplanted tumor cells were shorter than the mouse counterpart. We next analyzed blood cfDNA samples from hepatocellular carcinoma and prostate cancer patients and found that mt-cfDNA lengths were inversely related to tumor size as well as the concentration of circulating tumor DNA. Our study suggested that monitoring the size of mt-cfDNAs in cancer patients would be a useful way to estimate tumor burden and cancer progression.
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- 2019
14. Photo-Crosslinked Pro-Angiogenic Hydrogel Dressing for Wound Healing.
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Zhang, Wang, Qian, Shuyi, Chen, Jia, Jian, Tianshen, Wang, Xuechun, Zhu, Xianmin, Dong, Yixiao, and Fan, Guoping
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VASCULAR endothelial growth factors ,ENDOTHELIAL growth factors ,HYDROCOLLOID surgical dressings ,WOUND healing ,PEPTIDES ,SCANNING electron microscopes - Abstract
Severe burns are one of the most devastating injuries, in which sustained inflammation and ischemia often delay the healing process. Pro-angiogenic growth factors such as vascular endothelial growth factor (VEGF) have been widely studied for promoting wound healing. However, the short half-life and instability of VEGF limit its clinical applications. In this study, we develop a photo-crosslinked hydrogel wound dressing from methacrylate hyaluronic acid (MeHA) bonded with a pro-angiogenic prominin-1-binding peptide (PR1P). The materials were extruded in wound bed and in situ formed a wound dressing via exposure to short-time ultraviolet radiation. The study shows that the PR1P-bonded hydrogel significantly improves VEGF recruitment, tubular formation, and cell migration in vitro. Swelling, Scanning Electron Microscope, and mechanical tests indicate the peptide does not affect the overall mechanical and physical properties of the hydrogels. For in vivo studies, the PR1P-bonded hydrogel dressing enhances neovascularization and accelerates wound closure in both deep second-degree burn and full-thickness excisional wound models. The Western blot assay shows such benefits can be related to the activation of the VEGF–Akt signaling pathway. These results suggest this photo-crosslinked hydrogel dressing efficiently promotes VEGF recruitment and angiogenesis in skin regeneration, indicating its potential for clinical applications in wound healing. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Targeting Metabotropic Glutamate Receptor 7 Promotes Neurogenesis
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Zhao, Jian, primary, Wang, Ying, additional, Fang, Jing, additional, Hu, Ganlu, additional, Tang, Kailin, additional, Zeng, Xianglu, additional, Wang, Changzheng, additional, Yu, Yong-Chun, additional, Cao, Zhiwei, additional, Zeng, Tao, additional, and Fan, Guoping, additional
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- 2024
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16. Organoids as Novel Models for Embryo Implantation Study
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Wei, Yubao, Zhang, Cuilian, Fan, Guoping, and Meng, Li
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- 2021
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17. Simultaneous profiling of transcriptome and DNA methylome from a single cell
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Hu, Youjin, Huang, Kevin, An, Qin, Du, Guizhen, Hu, Ganlu, Xue, Jinfeng, Zhu, Xianmin, Wang, Cun-Yu, Xue, Zhigang, and Fan, Guoping
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Human Genome ,Biotechnology ,1.1 Normal biological development and functioning ,Aetiology ,Underpinning research ,2.1 Biological and endogenous factors ,Generic health relevance ,Animals ,Cells ,Cultured ,CpG Islands ,DNA Methylation ,Gene Expression Profiling ,Mice ,Mice ,Inbred C57BL ,Neurons ,Polymorphism ,Single Nucleotide ,Promoter Regions ,Genetic ,Sequence Analysis ,DNA ,Sequence Analysis ,RNA ,Single-Cell Analysis ,Transcriptome ,Single-cell methylome ,Single-cell transcriptome ,Sensory neurons ,Dorsal root ganglion ,Gene regulation ,Environmental Sciences ,Information and Computing Sciences ,Bioinformatics - Abstract
BackgroundSingle-cell transcriptome and single-cell methylome technologies have become powerful tools to study RNA and DNA methylation profiles of single cells at a genome-wide scale. A major challenge has been to understand the direct correlation of DNA methylation and gene expression within single-cells. Due to large cell-to-cell variability and the lack of direct measurements of transcriptome and methylome of the same cell, the association is still unclear.ResultsHere, we describe a novel method (scMT-seq) that simultaneously profiles both DNA methylome and transcriptome from the same cell. In sensory neurons, we consistently identify transcriptome and methylome heterogeneity among single cells but the majority of the expression variance is not explained by proximal promoter methylation, with the exception of genes that do not contain CpG islands. By contrast, gene body methylation is positively associated with gene expression for only those genes that contain a CpG island promoter. Furthermore, using single nucleotide polymorphism patterns from our hybrid mouse model, we also find positive correlation of allelic gene body methylation with allelic expression.ConclusionsOur method can be used to detect transcriptome, methylome, and single nucleotide polymorphism information within single cells to dissect the mechanisms of epigenetic gene regulation.
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- 2016
18. Single molecule RNA localization and translation in the mammalian oocyte and embryo
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Jansova, Denisa, Aleshkina, Daria, Jindrova, Anna, Iyyappan, Rajan, Qin, An, Fan, Guoping, and Susor, Andrej
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- 2021
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19. Integrating Complaint Analysis into Hospital Management: A Comparative Study of Surgical and Non-Surgical Complaints.
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Qin, Jinling, Lu, Bo, Li, Xiaoyu, Sun, Daofan, Liu, Rongjun, Wu, Yixiao, and Fan, Guoping
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Aims/Background: In an era where patient-centred care is paramount, effectively managing and analyzing hospital complaints is crucial for improving service quality and patient satisfaction. This study examines hospital complaints to enhance management practices by differentiating between surgery-related and non-surgery-related grievances. By identifying patterns in complaint types and outcomes, we aim to inform targeted quality improvement strategies that address specific patient concerns and boost operational efficiency. Methods: The study utilized data from an internal complaint management system over one year. Complaints were categorized as either surgery-related or non-surgery-related. Descriptive statistics and cross-tabulation analysis were employed to examine the data. The sample comprised 132 complaints, with 67 being surgery-related and 65 non-surgery-related. Results: The analysis revealed that surgery-related complaints frequently involved issues with 'Patient Communication' and 'Surgical Error', while non-surgery-related complaints were primarily about the 'Medical Treatment Process'. The Surgery Department received the highest number of complaints, indicating a critical area for intervention. Additionally, the correlation between complaint types and outcomes provided insights into potential areas for improvement. Conclusion: The findings highlight the need for targeted communication training and procedural enhancements in surgical departments. Non-surgical departments should focus on improving treatment protocols and transparency. These strategies can reduce complaints and improve patient satisfaction. Future research should develop and test interventions based on these insights to further enhance healthcare quality. [ABSTRACT FROM AUTHOR]
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- 2024
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20. Type 2 diabetes mellitus worsens the prognosis of intermediate-stage hepatocellular carcinoma after transarterial chemoembolization
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Liu, Guanghua, Xia, Fang, Fan, Guoping, Yu, Juming, Bao, Lei, Zhang, Caiyuan, Chi, Runmin, Zhang, Tingting, Wang, Lijun, Shen, Feng, and Wang, Dengbin
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- 2020
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21. Recent advances in preimplantation genetic diagnosis and screening
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Lu, Lina, Lv, Bo, Huang, Kevin, Xue, Zhigang, Zhu, Xianmin, and Fan, Guoping
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Reproductive Medicine ,Biomedical and Clinical Sciences ,Biological Sciences ,Biotechnology ,Infertility ,Abortion ,Spontaneous ,Aneuploidy ,Comparative Genomic Hybridization ,Embryo Transfer ,Female ,Fertilization in Vitro ,Genetic Testing ,Humans ,Pregnancy ,Preimplantation Diagnosis ,Preimplantation genetic diagnosis ,Preimplantation genetic screening ,In vitro fertilization ,Embryo biopsy ,Non-invasive testing ,Genetics ,Paediatrics and Reproductive Medicine ,Obstetrics & Reproductive Medicine ,Reproductive medicine - Abstract
Preimplantation genetic diagnosis/screening (PGD/PGS) aims to help couples lower the risks of transmitting genetic defects to their offspring, implantation failure, and/or miscarriage during in vitro fertilization (IVF) cycles. However, it is still being debated with regard to the practicality and diagnostic accuracy of PGD/PGS due to the concern of invasive biopsy and the potential mosaicism of embryos. Recently, several non-invasive and high-throughput assays have been developed to help overcome the challenges encountered in the conventional invasive biopsy and low-throughput analysis in PGD/PGS. In this mini-review, we will summarize the recent progresses of these new methods for PGD/PGS and discuss their potential applications in IVF clinics.
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- 2016
22. Reversible Regulation of Promoter and Enhancer Histone Landscape by DNA Methylation in Mouse Embryonic Stem Cells
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King, Andrew D, Huang, Kevin, Rubbi, Liudmilla, Liu, Shuo, Wang, Cun-Yu, Wang, Yinsheng, Pellegrini, Matteo, and Fan, Guoping
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Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Human Genome ,Stem Cell Research - Embryonic - Non-Human ,Stem Cell Research ,Generic health relevance ,Animals ,Cell Line ,DNA (Cytosine-5-)-Methyltransferases ,DNA Methylation ,Enhancer Elements ,Genetic ,Epigenesis ,Genetic ,Histone Code ,Histones ,Mice ,Mouse Embryonic Stem Cells ,Promoter Regions ,Genetic ,DNA methylation ,chromatin ,embryonic stem cells ,enhancers ,epigenetics ,gene regulation ,histone modifications ,polycomb ,promoters ,Biochemistry and Cell Biology ,Medical Physiology ,Biological sciences - Abstract
DNA methylation is one of a number of modes of epigenetic gene regulation. Here, we profile the DNA methylome, transcriptome, and global occupancy of histone modifications (H3K4me1, H3K4me3, H3K27me3, and H3K27ac) in a series of mouse embryonic stem cells (mESCs) with varying DNA methylation levels to study the effects of DNA methylation on deposition of histone modifications. We find that genome-wide DNA demethylation alters occupancy of histone modifications at both promoters and enhancers. This is reversed upon remethylation by Dnmt expression. DNA methylation promotes H3K27me3 deposition at bivalent promoters, while opposing H3K27me3 at silent promoters. DNA methylation also reversibly regulates H3K27ac and H3K27me3 at previously identified tissue-specific enhancers. These effects require DNMT catalytic activity. Collectively, our data show that DNA methylation is essential and instructive for deposition of specific histone modifications across regulatory regions, which together influences gene expression patterns in mESCs.
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- 2016
23. Single-cell RNA-seq reveals distinct injury responses in different types of DRG sensory neurons.
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Hu, Ganlu, Huang, Kevin, Hu, Youjin, Du, Guizhen, Xue, Zhigang, Zhu, Xianmin, and Fan, Guoping
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Ganglia ,Spinal ,Animals ,Mice ,Rats ,Gene Expression Profiling ,Sequence Analysis ,RNA ,Gene Expression Regulation ,Principal Component Analysis ,Female ,Male ,Gene Regulatory Networks ,Sensory Receptor Cells ,Single-Cell Analysis ,Peripheral Nerve Injuries ,Ganglia ,Spinal ,Sequence Analysis ,RNA ,Biochemistry and Cell Biology ,Other Physical Sciences - Abstract
Peripheral nerve injury leads to various injury-induced responses in sensory neurons including physiological pain, neuronal cell death, and nerve regeneration. In this study, we performed single-cell RNA-sequencing (scRNA-seq) analysis of mouse nonpeptidergic nociceptors (NP), peptidergic nociceptors (PEP), and large myelinated sensory neurons (LM) under both control and injury conditions at 3 days after sciatic nerve transection (SNT). After performing principle component and weighted gene co-expression network analysis, we categorized dorsal root ganglion (DRG) neurons into different subtypes and discovered co-regulated injury-response genes including novel regeneration associated genes (RAGs) in association with neuronal development, protein translation and cytoplasm transportation. In addition, we found significant up-regulation of the genes associated with cell death such as Pdcd2 in a subset of NP neurons after axotomy, implicating their actions in neuronal cell death upon nerve injury. Our study revealed the distinctive and sustained heterogeneity of transcriptomic responses to injury at single neuron level, implicating the involvement of different gene regulatory networks in nerve regeneration, neuronal cell death and neuropathy in different population of DRG neurons.
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- 2016
24. Methyltransferase Dnmt3a upregulates HDAC9 to deacetylate the kinase TBK1 for activation of antiviral innate immunity
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Li, Xia, Zhang, Qian, Ding, Yuanyuan, Liu, Yiqi, Zhao, Dezhi, Zhao, Kai, Shen, Qicong, Liu, Xingguang, Zhu, Xuhui, Li, Nan, Cheng, Zhongyi, Fan, Guoping, Wang, Qingqing, and Cao, Xuetao
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Medical Microbiology ,Biomedical and Clinical Sciences ,Biological Sciences ,Biodefense ,Vaccine Related ,Emerging Infectious Diseases ,Prevention ,Acetylation ,Animals ,DNA (Cytosine-5-)-Methyltransferases ,DNA Methyltransferase 3A ,Epigenesis ,Genetic ,HEK293 Cells ,Histone Deacetylases ,Humans ,Immunity ,Innate ,Interferon Type I ,Macrophages ,Male ,Mice ,Mice ,Inbred C57BL ,Mice ,Transgenic ,Protein Serine-Threonine Kinases ,RAW 264.7 Cells ,Receptors ,Pattern Recognition ,Repressor Proteins ,Rhabdoviridae Infections ,Signal Transduction ,Vesicular stomatitis Indiana virus ,Immunology ,Biochemistry and cell biology - Abstract
The DNA methyltransferase Dnmt3a has high expression in terminally differentiated macrophages; however, its role in innate immunity remains unknown. Here we report that deficiency in Dnmt3a selectively impaired the production of type I interferons triggered by pattern-recognition receptors (PRRs), but not that of the proinflammatory cytokines TNF and IL-6. Dnmt3a-deficient mice exhibited enhanced susceptibility to viral challenge. Dnmt3a did not directly regulate the transcription of genes encoding type I interferons; instead, it increased the production of type I interferons through an epigenetic mechanism by maintaining high expression of the histone deacetylase HDAC9. In turn, HDAC9 directly maintained the deacetylation status of the key PRR signaling molecule TBK1 and enhanced its kinase activity. Our data add mechanistic insight into the crosstalk between epigenetic modifications and post-translational modifications in the regulation of PRR signaling and activation of antiviral innate immune responses.
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- 2016
25. Functional Characterization of DNA Methylation in the Oligodendrocyte Lineage.
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Moyon, Sarah, Huynh, Jimmy L, Dutta, Dipankar, Zhang, Fan, Ma, Dan, Yoo, Seungyeul, Lawrence, Rebecca, Wegner, Michael, John, Gareth R, Emery, Ben, Lubetzki, Catherine, Franklin, Robin JM, Fan, Guoping, Zhu, Jun, Dupree, Jeffrey L, and Casaccia, Patrizia
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Biochemistry and Cell Biology ,Medical Physiology - Abstract
Oligodendrocytes derive from progenitors (OPCs) through the interplay of epigenomic and transcriptional events. By integrating high-resolution methylomics, RNA-sequencing, and multiple transgenic lines, this study defines the role of DNMT1 in developmental myelination. We detected hypermethylation of genes related to cell cycle and neurogenesis during differentiation of OPCs, yet genetic ablation of Dnmt1 resulted in inefficient OPC expansion and severe hypomyelination associated with ataxia and tremors in mice. This phenotype was not caused by lineage switch or massive apoptosis but was characterized by a profound defect of differentiation associated with changes in exon-skipping and intron-retention splicing events and by the activation of an endoplasmic reticulum stress response. Therefore, loss of Dnmt1 in OPCs is not sufficient to induce a lineage switch but acts as an important determinant of the coordination between RNA splicing and protein synthesis necessary for myelin formation.
- Published
- 2016
26. Simultaneous profiling of full-length RNA transcripts and chromatin accessibility within single cells of human retinal organoids
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Hu, Youjin, primary, Zhang, Shuyao, additional, Mo, Xinzhi, additional, Xiao, Yuhua, additional, Qiu, Yuanhui, additional, Zhong, Jiawei, additional, Chen, Zheyao, additional, Liu, Xu, additional, Chen, Xu, additional, Dai, Wangxuan, additional, Chen, Jia, additional, Jin, Xishan, additional, and Fan, Guoping, additional
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- 2023
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27. Supramolecular Nanosubstrate‐Mediated Delivery for Reprogramming and Transdifferentiation of Mammalian Cells
- Author
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Hou, Shuang, Choi, Jin-sil, Chen, Kuan-Ju, Zhang, Yang, Peng, Jinliang, Garcia, Mitch A, Yu, Jue-Hua, Thakore-Shah, Kaushali, Ro, Tracy, Chen, Jie-Fu, Peyda, Parham, Fan, Guoping, Pyle, April D, Wang, Hao, and Tseng, Hsian-Rong
- Subjects
Macromolecular and Materials Chemistry ,Organic Chemistry ,Chemical Sciences ,Stem Cell Research ,Cell Line ,Cell Transdifferentiation ,Cellular Reprogramming ,Cellular Reprogramming Techniques ,Fibroblasts ,Gene Transfer Techniques ,Genetic Vectors ,Humans ,Nanocapsules ,Nanotechnology ,Polymorphism ,Single Nucleotide ,cell reprogramming ,cell transdifferentiation ,nanoparticles ,nanosubstrates ,gene delivery ,supramolecular chemistry ,nanosubstrates ,gene delivery ,Nanoscience & Nanotechnology - Abstract
Supramolecular nanosubstrate-mediated delivery (SNSMD) leverages the power of molecular self-assembly and a nanostructured substrate platform for the low toxicity, highly efficient co-delivery of biological factors encapsulated in a nanovector. Human fibroblasts are successfully reprogrammed into induced pluripotent stems and transdifferentiated into induced neuronal-like cells.
- Published
- 2015
28. Stem cell-based therapy of corneal epithelial and endothelial diseases
- Author
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Yuan, Songtao and Fan, Guoping
- Subjects
Regenerative Medicine ,Transplantation ,Stem Cell Research ,Eye Disease and Disorders of Vision ,Stem Cell Research - Nonembryonic - Human ,Development of treatments and therapeutic interventions ,5.2 Cellular and gene therapies ,Eye ,Corneal Diseases ,Endothelium ,Corneal ,Epithelium ,Corneal ,Humans ,Stem Cell Transplantation ,Translational Research ,Biomedical ,cell transplantation ,corneal endothelium ,corneal transplantation ,limbal epithelial stem cells ,stem cell differentiation ,Medical Biotechnology ,Developmental Biology - Abstract
Corneal dysfunction is the second leading cause of blindness. Approximately 10 million patients worldwide are affected by some form of corneal disease. More than 50,000 cornea transplants are performed every year, but this procedure is limited by cornea donation availability. Recently, new cell replacement procedures have been developed to treat a variety of corneal diseases. This review will focus on the recent advances in the use of limbal epithelial stem cells (LESCs) to treat corneal epithelial cell deficiency and improvements in replacing dysfunctional corneal endothelial cells (CECs) with exogenous CECs. Several protocols have been developed to differentiate pluripotent stem cells into LESC- or CEC-like cells, potentially yielding an unlimited source for the cell replacement therapy of corneal diseases.
- Published
- 2015
29. Role of Tet1 and 5-hydroxymethylcytosine in cocaine action.
- Author
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Feng, Jian, Shao, Ningyi, Szulwach, Keith E, Vialou, Vincent, Huynh, Jimmy, Zhong, Chun, Le, Thuc, Ferguson, Deveroux, Cahill, Michael E, Li, Yujing, Koo, Ja Wook, Ribeiro, Efrain, Labonte, Benoit, Laitman, Benjamin M, Estey, David, Stockman, Victoria, Kennedy, Pamela, Couroussé, Thomas, Mensah, Isaac, Turecki, Gustavo, Faull, Kym F, Ming, Guo-li, Song, Hongjun, Fan, Guoping, Casaccia, Patrizia, Shen, Li, Jin, Peng, and Nestler, Eric J
- Subjects
Nucleus Accumbens ,Animals ,Mice ,Inbred C57BL ,Mice ,Cocaine ,Cytosine ,DNA-Binding Proteins ,Proto-Oncogene Proteins ,Behavior ,Animal ,Gene Expression ,Down-Regulation ,Epigenesis ,Genetic ,Male ,5-Methylcytosine ,Inbred C57BL ,Behavior ,Animal ,Epigenesis ,Genetic ,Neurology & Neurosurgery ,Neurosciences ,Cognitive Sciences ,Psychology - Abstract
Ten-eleven translocation (TET) enzymes mediate the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is enriched in brain, and its ultimate DNA demethylation. However, the influence of TET and 5hmC on gene transcription in brain remains elusive. We found that ten-eleven translocation protein 1 (TET1) was downregulated in mouse nucleus accumbens (NAc), a key brain reward structure, by repeated cocaine administration, which enhanced behavioral responses to cocaine. We then identified 5hmC induction in putative enhancers and coding regions of genes that have pivotal roles in drug addiction. Such induction of 5hmC, which occurred similarly following TET1 knockdown alone, correlated with increased expression of these genes as well as with their alternative splicing in response to cocaine administration. In addition, 5hmC alterations at certain loci persisted for at least 1 month after cocaine exposure. Together, these reveal a previously unknown epigenetic mechanism of cocaine action and provide new insight into how 5hmC regulates transcription in brain in vivo.
- Published
- 2015
30. Selective demethylation and altered gene expression are associated with ICF syndrome in human-induced pluripotent stem cells and mesenchymal stem cells
- Author
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Huang, Kevin, Wu, Zhourui, Liu, Zhenshan, Hu, Ganlu, Yu, Juehua, Chang, Kai H, Kim, Kee-Pyo, Le, Thuc, Faull, Kym F, Rao, Nagesh, Gennery, Andrew, Xue, Zhigang, Wang, Cun-yu, Pellegrini, Matteo, and Fan, Guoping
- Subjects
Stem Cell Research - Nonembryonic - Human ,Regenerative Medicine ,Pediatric ,Genetics ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Stem Cell Research ,Stem Cell Research - Induced Pluripotent Stem Cell ,Human Genome ,Biotechnology ,2.1 Biological and endogenous factors ,Aetiology ,Cell Differentiation ,DNA (Cytosine-5-)-Methyltransferases ,DNA Methylation ,Enhancer Elements ,Genetic ,Epigenesis ,Genetic ,Fibroblasts ,Genome ,Human ,Humans ,Immunologic Deficiency Syndromes ,Induced Pluripotent Stem Cells ,Mesenchymal Stem Cells ,Promoter Regions ,Genetic ,Biological Sciences ,Medical and Health Sciences ,Genetics & Heredity - Abstract
Immunodeficiency, centromeric instability and facial anomalies type I (ICF1) syndrome is a rare genetic disease caused by mutations in DNA methyltransferase (DNMT) 3B, a de novo DNA methyltransferase. However, the molecular basis of how DNMT3B deficiency leads to ICF1 pathogenesis is unclear. Induced pluripotent stem cell (iPSC) technology facilitates the study of early human developmental diseases via facile in vitro paradigms. Here, we generate iPSCs from ICF Type 1 syndrome patient fibroblasts followed by directed differentiation of ICF1-iPSCs to mesenchymal stem cells (MSCs). By performing genome-scale bisulfite sequencing, we find that DNMT3B-deficient iPSCs exhibit global loss of non-CG methylation and select CG hypomethylation at gene promoters and enhancers. Further unbiased scanning of ICF1-iPSC methylomes also identifies large megabase regions of CG hypomethylation typically localized in centromeric and subtelomeric regions. RNA sequencing of ICF1 and control iPSCs reveals abnormal gene expression in ICF1-iPSCs relevant to ICF syndrome phenotypes, some directly associated with promoter or enhancer hypomethylation. Upon differentiation of ICF1 iPSCs to MSCs, we find virtually all CG hypomethylated regions remained hypomethylated when compared with either wild-type iPSC-derived MSCs or primary bone-marrow MSCs. Collectively, our results show specific methylome and transcriptome defects in both ICF1-iPSCs and differentiated somatic cell lineages, providing a valuable stem cell system for further in vitro study of the molecular pathogenesis of ICF1 syndrome. GEO accession number: GSE46030.
- Published
- 2014
31. Alpha-fetoprotein response following transarterial chemoembolization indicates improved survival for intermediate-stage hepatocellular carcinoma
- Author
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Liu, Guanghua, Ouyang, Qiang, Xia, Fang, Fan, Guoping, Yu, Juming, Zhang, Caiyuan, and Wang, Dengbin
- Published
- 2019
- Full Text
- View/download PDF
32. The Naive State of Human Pluripotent Stem Cells: A Synthesis of Stem Cell and Preimplantation Embryo Transcriptome Analyses
- Author
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Huang, Kevin, Maruyama, Toru, and Fan, Guoping
- Subjects
Genetics ,Stem Cell Research - Nonembryonic - Human ,Biotechnology ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Stem Cell Research ,Stem Cell Research - Embryonic - Human ,Regenerative Medicine ,Stem Cell Research - Induced Pluripotent Stem Cell ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Animals ,Blastocyst ,Gene Expression Profiling ,Gene Regulatory Networks ,Genome ,Humans ,Mitochondria ,Pluripotent Stem Cells ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Here we use a systems biology approach to comprehensively assess the conservation of gene networks in naive pluripotent stem cells (PSCs) with preimplantation embryos. While gene networks in murine naive and primed pluripotent states are reproducible across data sets, different sources of human stem cells display high degrees of variation, partly reflecting disparities in culture conditions. Finally, naive gene networks between human and mouse PSCs are not well conserved and better resemble their respective blastocysts.
- Published
- 2014
33. Common dysregulation network in the human prefrontal cortex underlies two neurodegenerative diseases.
- Author
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Narayanan, Manikandan, Huynh, Jimmy L, Wang, Kai, Yang, Xia, Yoo, Seungyeul, McElwee, Joshua, Zhang, Bin, Zhang, Chunsheng, Lamb, John R, Xie, Tao, Suver, Christine, Molony, Cliona, Melquist, Stacey, Johnson, Andrew D, Fan, Guoping, Stone, David J, Schadt, Eric E, Casaccia, Patrizia, Emilsson, Valur, and Zhu, Jun
- Subjects
Prefrontal Cortex ,Chromatin ,Animals ,Mice ,Knockout ,Humans ,Mice ,Huntington Disease ,Dementia ,Alzheimer Disease ,Autopsy ,Case-Control Studies ,Reproducibility of Results ,Gene Expression Profiling ,Gene Expression Regulation ,Gene Regulatory Networks ,DNA (Cytosine-5-)-Methyltransferase 1 ,DNA (Cytosine-5-)-Methyltransferases ,differential co‐expression ,dysregulatory gene networks ,epigenetic regulation of neural differentiation ,network alignment ,neurodegenerative diseases ,differential co-expression ,Knockout ,DNA (Cytosine-5-)-Methyltransferase ,Bioinformatics ,Biochemistry and Cell Biology ,Other Biological Sciences - Abstract
Using expression profiles from postmortem prefrontal cortex samples of 624 dementia patients and non-demented controls, we investigated global disruptions in the co-regulation of genes in two neurodegenerative diseases, late-onset Alzheimer's disease (AD) and Huntington's disease (HD). We identified networks of differentially co-expressed (DC) gene pairs that either gained or lost correlation in disease cases relative to the control group, with the former dominant for both AD and HD and both patterns replicating in independent human cohorts of AD and aging. When aligning networks of DC patterns and physical interactions, we identified a 242-gene subnetwork enriched for independent AD/HD signatures. This subnetwork revealed a surprising dichotomy of gained/lost correlations among two inter-connected processes, chromatin organization and neural differentiation, and included DNA methyltransferases, DNMT1 and DNMT3A, of which we predicted the former but not latter as a key regulator. To validate the inter-connection of these two processes and our key regulator prediction, we generated two brain-specific knockout (KO) mice and show that Dnmt1 KO signature significantly overlaps with the subnetwork (P = 3.1 × 10(-12)), while Dnmt3a KO signature does not (P = 0.017).
- Published
- 2014
34. A Panel of CpG Methylation Sites Distinguishes Human Embryonic Stem Cells and Induced Pluripotent Stem Cells
- Author
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Huang, Kevin, Shen, Yin, Xue, Zhigang, Bibikova, Marina, April, Craig, Liu, Zhenshan, Cheng, Linzhao, Nagy, Andras, Pellegrini, Matteo, Fan, Jian-Bing, and Fan, Guoping
- Subjects
Biological Sciences ,Genetics ,Stem Cell Research - Induced Pluripotent Stem Cell ,Stem Cell Research ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Stem Cell Research - Embryonic - Human ,Regenerative Medicine ,Generic health relevance ,Cells ,Cultured ,CpG Islands ,DNA (Cytosine-5-)-Methyltransferases ,DNA Methylation ,Embryonic Stem Cells ,Humans ,Induced Pluripotent Stem Cells ,Promoter Regions ,Genetic ,Support Vector Machine ,Transcriptome ,DNA Methyltransferase 3B ,Biochemistry and Cell Biology ,Clinical Sciences ,Biochemistry and cell biology - Abstract
Whether human induced pluripotent stem cells (hiPSCs) are epigenetically identical to human embryonic stem cells (hESCs) has been debated in the stem cell field. In this study, we analyzed DNA methylation patterns in a large number of hiPSCs (n = 114) and hESCs (n = 155), and identified a panel of 82 CpG methylation sites that can distinguish hiPSCs from hESCs with high accuracy. We show that 12 out of the 82 CpG sites were subject to hypermethylation in part by DNMT3B. Notably, DNMT3B contributes directly to aberrant hypermethylation and silencing of the signature gene, TCERG1L. Overall, we conclude that DNMT3B is involved in a wave of de novo methylation during reprogramming, a portion of which contributes to the unique hiPSC methylation signature. These 82 CpG methylation sites may be useful as biomarkers to distinguish between hiPSCs and hESCs.
- Published
- 2014
35. PIAS1 regulates breast tumorigenesis through selective epigenetic gene silencing.
- Author
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Liu, Bin, Tahk, Samuel, Yee, Kathleen M, Yang, Randy, Yang, Yonghui, Mackie, Ryan, Hsu, Cary, Chernishof, Vasili, O'Brien, Neil, Jin, Yusheng, Fan, Guoping, Lane, Timothy F, Rao, Jianyu, Slamon, Dennis, and Shuai, Ke
- Subjects
Breast ,Cell Line ,Tumor ,Animals ,Humans ,Mice ,SCID ,Breast Neoplasms ,Ubiquitin-Protein Ligases ,Proto-Oncogene Proteins ,Receptors ,Estrogen ,Small Ubiquitin-Related Modifier Proteins ,DNA Methylation ,Epigenesis ,Genetic ,Gene Expression Regulation ,Neoplastic ,Gene Silencing ,Female ,Protein Inhibitors of Activated STAT ,Wnt Proteins ,Cyclin D2 ,Carcinogenesis ,Wnt-5a Protein ,Cell Line ,Tumor ,Mice ,SCID ,Receptors ,Estrogen ,Epigenesis ,Genetic ,Gene Expression Regulation ,Neoplastic ,General Science & Technology - Abstract
Epigenetic gene silencing by histone modifications and DNA methylation is essential for cancer development. The molecular mechanism that promotes selective epigenetic changes during tumorigenesis is not understood. We report here that the PIAS1 SUMO ligase is involved in the progression of breast tumorigenesis. Elevated PIAS1 expression was observed in breast tumor samples. PIAS1 knockdown in breast cancer cells reduced the subpopulation of tumor-initiating cells, and inhibited breast tumor growth in vivo. PIAS1 acts by delineating histone modifications and DNA methylation to silence the expression of a subset of clinically relevant genes, including breast cancer DNA methylation signature genes such as cyclin D2 and estrogen receptor, and breast tumor suppressor WNT5A. Our studies identify a novel epigenetic mechanism that regulates breast tumorigenesis through selective gene silencing.
- Published
- 2014
36. Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing.
- Author
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Xue, Zhigang, Huang, Kevin, Cai, Chaochao, Cai, Lingbo, Jiang, Chun-yan, Feng, Yun, Liu, Zhenshan, Zeng, Qiao, Cheng, Liming, Sun, Yi, Liu, Jia-yin, Horvath, Steve, and Fan, Guoping
- Subjects
Alleles ,Animals ,Blastocyst ,Cell Cycle ,Embryo ,Mammalian ,Embryonic Development ,Gene Expression Profiling ,Gene Expression Regulation ,Developmental ,Humans ,Mice ,Morula ,Oocytes ,Sequence Analysis ,RNA ,Single-Cell Analysis - Abstract
Mammalian pre-implantation development is a complex process involving dramatic changes in the transcriptional architecture. We report here a comprehensive analysis of transcriptome dynamics from oocyte to morula in both human and mouse embryos, using single-cell RNA sequencing. Based on single-nucleotide variants in human blastomere messenger RNAs and paternal-specific single-nucleotide polymorphisms, we identify novel stage-specific monoallelic expression patterns for a significant portion of polymorphic gene transcripts (25 to 53%). By weighted gene co-expression network analysis, we find that each developmental stage can be delineated concisely by a small number of functional modules of co-expressed genes. This result indicates a sequential order of transcriptional changes in pathways of cell cycle, gene regulation, translation and metabolism, acting in a step-wise fashion from cleavage to morula. Cross-species comparisons with mouse pre-implantation embryos reveal that the majority of human stage-specific modules (7 out of 9) are notably preserved, but developmental specificity and timing differ between human and mouse. Furthermore, we identify conserved key members (or hub genes) of the human and mouse networks. These genes represent novel candidates that are likely to be key in driving mammalian pre-implantation development. Together, the results provide a valuable resource to dissect gene regulatory mechanisms underlying progressive development of early mammalian embryos.
- Published
- 2013
37. Multimodal imaging of the retina and choroid in healthy Macaca fascicularis at different ages
- Author
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Fan, Shuxin, Ding, Xiaoyan, Rao, Pinhong, Zheng, Yingfeng, Mao, Fuxiang, Hu, Youjin, Liu, Xialin, and Fan, Guoping
- Published
- 2019
- Full Text
- View/download PDF
38. Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1
- Author
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Li, Yingfeng, Zhang, Zhuqiang, Chen, Jiayu, Liu, Wenqiang, Lai, Weiyi, Liu, Baodong, Li, Xiang, Liu, Liping, Xu, Shaohua, Dong, Qiang, Wang, Mingzhu, Duan, Xiaoya, Tan, Jiajun, Zheng, Yong, Zhang, Pumin, Fan, Guoping, Wong, Jiemin, Xu, Guo-Liang, Wang, Zhigao, Wang, Hailin, Gao, Shaorong, and Zhu, Bing
- Published
- 2018
- Full Text
- View/download PDF
39. Juvenile neurogenesis makes essential contributions to adult brain structure and plays a sex-dependent role in fear memories
- Author
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Cushman, Jesse D, Maldonado, Jose, Kwon, Eunice E, Garcia, A Denise, Fan, Guoping, Imura, Tetsuya, Sofroniew, Michael V, and Fanselow, Michael S
- Subjects
Behavioral and Social Science ,Stem Cell Research - Nonembryonic - Non-Human ,Neurosciences ,Pediatric ,Stem Cell Research ,Mental Health ,Basic Behavioral and Social Science ,Underpinning research ,1.1 Normal biological development and functioning ,Neurological ,adult neurogenesis ,juvenile neurogenesis ,postnatal neurogenesis ,hippocampus ,olfactory bulb ,learning and memory ,sex difference ,fear conditioning ,Psychology ,Cognitive Sciences - Abstract
Postnatal neurogenesis (PNN) contributes neurons to olfactory bulb (OB) and dentate gyrus (DG) throughout juvenile development, but the quantitative amount, temporal dynamics and functional roles of this contribution have not been defined. By using transgenic mouse models for cell lineage tracing and conditional cell ablation, we found that juvenile neurogenesis gradually increased the total number of granule neurons by approximately 40% in OB, and by 25% in DG, between 2 weeks and 2 months of age, and that total numbers remained stable thereafter. These findings indicate that the overwhelming majority of net postnatal neuronal addition in these regions occurs during the juvenile period and that adult neurogenesis contributes primarily to replacement of granule cells in both regions. Behavioral analysis in our conditional cell ablation mouse model showed that complete loss of PNN throughout both the juvenile and young adult period produced a specific set of sex-dependent cognitive changes. We observed normal hippocampus-independent delay fear conditioning, but excessive generalization of fear to a novel auditory stimulus, which is consistent with a role for PNN in psychopathology. Standard contextual fear conditioning was intact, however, pre-exposure dependent contextual fear was impaired suggesting a specific role for PNN in incidental contextual learning. Contextual discrimination between two highly similar contexts was enhanced; suggesting either enhanced contextual pattern separation or impaired temporal integration. We also observed a reduced reliance on olfactory cues, consistent with a role for OB PNN in the efficient processing of olfactory information. Thus, juvenile neurogenesis adds substantively to the total numbers of granule neurons in OB and DG during periods of critical juvenile behavioral development, including weaning, early social interactions and sexual maturation, and plays a sex-dependent role in fear memories.
- Published
- 2012
40. Signed weighted gene co-expression network analysis of transcriptional regulation in murine embryonic stem cells
- Author
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Mason, Mike J, Fan, Guoping, Plath, Kathrin, Zhou, Qing, and Horvath, Steve
- Abstract
Abstract Background Recent work has revealed that a core group of transcription factors (TFs) regulates the key characteristics of embryonic stem (ES) cells: pluripotency and self-renewal. Current efforts focus on identifying genes that play important roles in maintaining pluripotency and self-renewal in ES cells and aim to understand the interactions among these genes. To that end, we investigated the use of unsigned and signed network analysis to identify pluripotency and differentiation related genes. Results We show that signed networks provide a better systems level understanding of the regulatory mechanisms of ES cells than unsigned networks, using two independent murine ES cell expression data sets. Specifically, using signed weighted gene co-expression network analysis (WGCNA), we found a pluripotency module and a differentiation module, which are not identified in unsigned networks. We confirmed the importance of these modules by incorporating genome-wide TF binding data for key ES cell regulators. Interestingly, we find that the pluripotency module is enriched with genes related to DNA damage repair and mitochondrial function in addition to transcriptional regulation. Using a connectivity measure of module membership, we not only identify known regulators of ES cells but also show that Mrpl15, Msh6, Nrf1, Nup133, Ppif, Rbpj, Sh3gl2, and Zfp39, among other genes, have important roles in maintaining ES cell pluripotency and self-renewal. We also report highly significant relationships between module membership and epigenetic modifications (histone modifications and promoter CpG methylation status), which are known to play a role in controlling gene expression during ES cell self-renewal and differentiation. Conclusion Our systems biologic re-analysis of gene expression, transcription factor binding, epigenetic and gene ontology data provides a novel integrative view of ES cell biology.
- Published
- 2009
41. DNA Methylation-Related Chromatin Remodeling in Activity-Dependent Bdnf Gene Regulation
- Author
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Martinowich, Keri, Hattori, Daisuke, Wu, Hao, Fouse, Shaun, He, Fei, Hu, Yan, Fan, Guoping, and Sun, Yi E.
- Published
- 2003
42. Single-cell RNA cap and tail sequencing (scRCAT-seq) reveals subtype-specific isoforms differing in transcript demarcation
- Author
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Hu, Youjin, Zhong, Jiawei, Xiao, Yuhua, Xing, Zheng, Sheu, Katherine, Fan, Shuxin, An, Qin, Qiu, Yuanhui, Zheng, Yingfeng, Liu, Xialin, Fan, Guoping, and Liu, Yizhi
- Published
- 2020
- Full Text
- View/download PDF
43. Single‐Cell RNA‐Sequencing Provides Insight into Skeletal Muscle Evolution during the Selection of Muscle Characteristics.
- Author
-
Xu, Doudou, Wan, Boyang, Qiu, Kai, Wang, Yubo, Zhang, Xin, Jiao, Ning, Yan, Enfa, Wu, Jiangwei, Yu, Run, Gao, Shuai, Du, Min, Liu, Chousheng, Li, Mingzhou, Fan, Guoping, and Yin, Jingdong
- Subjects
RNA sequencing ,ARTIFICIAL cells ,WILD boar ,CELL populations ,SEQUENCE analysis - Abstract
Skeletal muscle comprises a large, heterogeneous assortment of cell populations that interact to maintain muscle homeostasis, but little is known about the mechanism that controls myogenic development in response to artificial selection. Different pig (Sus scrofa) breeds exhibit distinct muscle phenotypes resulting from domestication and selective breeding. Using unbiased single‐cell transcriptomic sequencing analysis (scRNA‐seq), the impact of artificial selection on cell profiles is investigated in neonatal skeletal muscle of pigs. This work provides panoramic muscle‐resident cell profiles and identifies novel and breed‐specific cells, mapping them on pseudotime trajectories. Artificial selection has elicited significant changes in muscle‐resident cell profiles, while conserving signs of generational environmental challenges. These results suggest that fibro‐adipogenic progenitors serve as a cellular interaction hub and that specific transcription factors identified here may serve as candidate target regulons for the pursuit of a specific muscle phenotype. Furthermore, a cross‐species comparison of humans, mice, and pigs illustrates the conservation and divergence of mammalian muscle ontology. The findings of this study reveal shifts in cellular heterogeneity, novel cell subpopulations, and their interactions that may greatly facilitate the understanding of the mechanism underlying divergent muscle phenotypes arising from artificial selection. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
44. Tunable Hydrogel Confinement via On-Chip 3D Printing for Studying Cancer Cell Migration.
- Author
-
Qian, Shuyi, Dong, Yixiao, Qu, Ju, Wang, Xuechun, Zhang, Wang, Chen, Jia, Xu, Fan, Cui, Meihua, Giomo, Monica, Liao, Chenhan, Hu, Manli, Xu, Juan, Hu, Ganlu, Zheng, Jie, Zhu, Xianmin, Urciuolo, Anna, Fan, Guoping, and Elvassore, Nicola
- Published
- 2023
- Full Text
- View/download PDF
45. Simultaneous Profiling of mRNA Transcriptome and DNA Methylome from a Single Cell
- Author
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Hu, Youjin, primary, An, Qin, additional, Guo, Ying, additional, Zhong, Jiawei, additional, Fan, Shuxin, additional, Rao, Pinhong, additional, Liu, Xialin, additional, Liu, Yizhi, additional, and Fan, Guoping, additional
- Published
- 2019
- Full Text
- View/download PDF
46. DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling
- Author
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Fan, Guoping, Martinowich, K, Chin, M H, He, F, Fouse, S D, Hutnick, L, Hattori, D, Ge, W H, Shen, Y, Hao, W, ten Hoeve, J, Shuai, K, and Sun, Y E
- Subjects
Dnmt1 ,CpG methylation ,neural differentiation ,STAT1 ,chromatin remodeling ,MeCP2 ,histone modification ,mouse - Abstract
DNA methylation is a major epigenetic factor that has been postulated to regulate cell lineage differentiation. We report here that conditional gene deletion of the maintenance DNA methyltransferase I (Dnmt1) in neural progenitor cells (NPCs) results in DNA hypomethylation and precocious astroglial differentiation. The developmentally regulated demethylation of astrocyte marker genes as well as genes encoding the crucial components of the gliogenic JAK-STAT pathway is accelerated in Dnmt1(-/-) NPCs. Through a chromatin remodeling process, demethylation of genes in the JAK-STAT pathway leads to an enhanced activation of STATs, which in turn triggers astrocyte differentiation. Our study suggests that during the neurogenic period, DNA methylation inhibits not only astroglial marker genes but also genes that are essential for JAK-STAT signaling. Thus, demethylation of these two groups of genes and subsequent elevation of STAT activity are key mechanisms that control the timing and magnitude of astroglial differentiation.
- Published
- 2005
47. Establishment of human-embryonic-stem-cell line from mosaic trisomy 9 embryo
- Author
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Huang, Boxian, Jiang, Chunyan, Chen, Aiqin, Cui, Yugui, Xie, Jiazi, Shen, Jiandong, Chen, Juan, Cai, Lingbo, Liao, Tingting, Ning, Song, Jiang, Shi-Wen, Fan, Guoping, Qin, Lianju, and Liu, Jiayin
- Published
- 2015
- Full Text
- View/download PDF
48. Bisphenol A Represses Dopaminergic Neuron Differentiation from Human Embryonic Stem Cells through Downregulating the Expression of Insulin-like Growth Factor 1
- Author
-
Huang, Boxian, Ning, Song, Zhang, Qinjing, Chen, Aiqin, Jiang, Chunyan, Cui, Yugui, Hu, Jian, Li, Hong, Fan, Guoping, Qin, Lianju, and Liu, Jiayin
- Published
- 2017
- Full Text
- View/download PDF
49. Structured Phase Retrieval-aided Channel Estimation for Millimeter-Wave/Sub-Terahertz MIMO Systems
- Author
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Liu, Kai-Hui, primary, Li, Xiangning, additional, Zhao, Haiyang, additional, and Fan, Guoping, additional
- Published
- 2022
- Full Text
- View/download PDF
50. DNA methylation in small cell lung cancer.
- Author
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Zhu, Xianmin, Gao, Yuehua, Feng, Yimiao, Zheng, Jie, Dong, Yixiao, Zhang, Peng, Zhu, Yuming, and Fan, Guoping
- Subjects
SMALL cell lung cancer ,CIRCULATING tumor DNA ,DNA methylation ,TUMOR suppressor genes ,CARCINOID ,REGULATOR genes - Abstract
Small cell lung cancer (SCLC) originates from pulmonary neuroendocrine cells and accounts for approximately 15% of lung cancer incidents. Patients with SCLC have a very low survival rate due to fast progression and early metastasis. Despite the recent approval of immune checkpoint blockade for treatment of SCLC by US FDA, conventional platinum chemotherapy remains the first‐line treatment which always develops quick drug resistance. To define targets for diagnosis and treatment, SCLC has been categorized by different molecular markers. The most popular markers include genomic mutations in tumour suppressor genes such as TP53 and RB1 and expression of lineage‐specific transcription factors (TFs), that is ASCL1, NEUROD1, POU2F3 and YAP1. As DNA methylation is an important hallmark of cancer, efforts were made to investigate the mechanisms of DNA methylation involved in SCLC progression. Indeed, SCLC has distinct pattern of DNA methylation due to its different features compared to non‐SCLC and other tumours. In this review, we summarized the mechanisms of DNA methylation in SCLC which are associated with lineage‐specific TFs, cell proliferation, anti‐apoptosis, drug resistance, immune evasion and metastasis. We foresaw the challenges of applying DNA methylation in clinical diagnosis and treatment and discussed new approaches and technologies to overcome them. Combined with other gene regulatory information such as transcription and histone modification, DNA methylation/hydroxymethylation in SCLC will be resolved at single‐cell resolution to dissect the tumour microenvironment. The huge multiomics data will be processed and integrated with clinical data such as clinical images and pathological histochemistry by artificial intelligence and cloud computing. Circulating cell‐free DNA methylation will greatly enhance early diagnosis and prognosis prediction. New organoid and organ chip models will break through the obstacles of sampling limitation, faithfully simulate the physiology of human tissues and enable examining spatiotemporal DNA methylation during SCLC progression. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
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