Human Brain Organoids Reveal Accelerated Development of Cortical Neuron Classes As a Shared Feature of Autism Risk Genes
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Identifying MMP14 and COL12A1 As a Potential Combination of Prognostic Biomarkers in Pancreatic Ductal Adenocarcinoma Using Integrated Bioinformatics Analysis
Identifying MMP14 and COL12A1 as a potential combination of prognostic biomarkers in pancreatic ductal adenocarcinoma using integrated bioinformatics analysis Jingyi Ding1, Yanxi Liu2 and Yu Lai3 1 Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China 2 University of California, Los Angeles, Los Angeles, CA, United States of America 3 School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China ABSTRACT Background. Pancreatic ductal adenocarcinoma (PDAC) is a fatal malignant neo- plasm. It is necessary to improve the understanding of the underlying molecular mechanisms and identify the key genes and signaling pathways involved in PDAC. Methods. The microarray datasets GSE28735, GSE62165, and GSE91035 were down- loaded from the Gene Expression Omnibus. Differentially expressed genes (DEGs) were identified by integrated bioinformatics analysis, including protein–protein interaction (PPI) network, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The PPI network was established using the Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. GO functional annotation and KEGG pathway analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery. Hub genes were validated via the Gene Expression Profiling Interactive Analysis tool (GEPIA) and the Human Protein Atlas (HPA) website. Results. A total of 263 DEGs (167 upregulated and 96 downregulated) were common to the three datasets. We used STRING and Cytoscape software to establish the PPI Submitted 25 August 2020 network and then identified key modules. From the PPI network, 225 nodes and 803 Accepted 2 November 2020 edges were selected. The most significant module, which comprised 11 DEGs, was Published 23 November 2020 identified using the Molecular Complex Detection plugin. -
CHL1 and Nrcam Are Primarily Expressed in Low Grade Pediatric
Open Med. 2019; 14: 920-927 Research Article Robin Wachowiak, Steffi Mayer, Anne Suttkus, Illya Martynov, Martin Lacher, Nathaniel Melling, Jakob R. Izbicki, Michael Tachezy CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma https://doi.org/10.1515/med-2019-0109 Keywords: CHL1; NrCAM; Neuroblastoma; Immunohisto- received November 7, 2018; accepted October 19, 2019 chemistry; Tumor markers; Neuropathology Abstract: Background. Neural cell adhesion molecules like close homolog of L1 protein (CHL1) and neuronal glia related cell adhesion molecule (NrCAM) play an impor- tant role in development and regeneration of the central 1 Introduction nervous system. However, they are also associated with Neuroblastoma is an embryonic malignancy deriving cancerogenesis and progression in adult malignancies, from neural crest cells that undergo rapid differentia- thus gain increasing importance in cancer research. We tion during fetal development. As the transition from therefore studied the expression of CHL1 and NrCAM normal to malignant tissue can occur in multiple steps, according to the course of disease in children with neu- its phenotype is highly heterogeneous [1]. Although pro- roblastoma. gress has been made in the treatment of neuroblastoma, Methods. CHL1 and NrCAM expression levels were histo- the outcome of children at high risk remains poor with a logically assessed by tissue microarrays from surgically long-term survival as low as 50 % [2]. Different parameters resected neuroblastoma specimens of 56 children. Expres- such as age, stage and chromosomal aberrations have an sion of both markers was correlated to demographics as impact on prognosis. Still, there is an ongoing need for well as clinical data including metastatic dissemination tumor markers, which allow a better determination of the and survival. -
Broad and Thematic Remodeling of the Surface Glycoproteome on Isogenic
bioRxiv preprint doi: https://doi.org/10.1101/808139; this version posted October 17, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Broad and thematic remodeling of the surface glycoproteome on isogenic cells transformed with driving proliferative oncogenes Kevin K. Leung1,5, Gary M. Wilson2,5, Lisa L. Kirkemo1, Nicholas M. Riley2,4, Joshua J. Coon2,3, James A. Wells1* 1Department of Pharmaceutical Chemistry, UCSF, San Francisco, CA, USA Departments of Chemistry2 and Biomolecular Chemistry3, University of Wisconsin- Madison, Madison, WI, 53706, USA 4Present address Department of Chemistry, Stanford University, Stanford, CA, 94305, USA 5These authors contributed equally *To whom correspondence should be addressed bioRxiv preprint doi: https://doi.org/10.1101/808139; this version posted October 17, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Abstract: The cell surface proteome, the surfaceome, is the interface for engaging the extracellular space in normal and cancer cells. Here We apply quantitative proteomics of N-linked glycoproteins to reveal how a collection of some 700 surface proteins is dramatically remodeled in an isogenic breast epithelial cell line stably expressing any of six of the most prominent proliferative oncogenes, including the receptor tyrosine kinases, EGFR and HER2, and downstream signaling partners such as KRAS, BRAF, MEK and AKT. -
Identification of Potential Biomarkers and Drugs for Papillary Thyroid Cancer Based on Gene Expression Profile Analysis
MOLECULAR MEDICINE REPORTS 14: 5041-5048, 2016 Identification of potential biomarkers and drugs for papillary thyroid cancer based on gene expression profile analysis TING QU1*, YAN-PING LI2*, XIAO-HONG LI1 and YAN CHEN1 Departments of 1Pharmacy and 2Endodontics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China Received September 17, 2015; Accepted September 29, 2016 DOI: 10.3892/mmr.2016.5855 Abstract. The present study aimed to systematically examine sition and responding to steroid hormone stimuli, respectively. the molecular mechanisms of papillary thyroid cancer (PTC), Ocriplasmin, β-mercaptoethanol and recombinant α 1-anti- and identify potential biomarkers and drugs for the treatment trypsin may be potential drugs for the treatment of PTC. of PTC. Two microarray data sets (GSE3467 and GSE3678), containing 16 PTC samples and 16 paired normal samples, Introduction were downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) were Thyroid cancer is one of the most common types of endocrine identified using the Linear Models for Microarray Analysis malignancy, the incidence rate of which has rapidly increased package. Subsequently, the common DEGs were screened for during previous years (1,2). It has been estimated that the functional and pathway enrichment analysis using the Database annual number of cases of thyroid cancer diagnosed in the for Annotation Visualization and Integrated Discovery. The USA and the associated mortality rate are 12.9/100,000 -
Supplementary Table 1: Adhesion Genes Data Set
Supplementary Table 1: Adhesion genes data set PROBE Entrez Gene ID Celera Gene ID Gene_Symbol Gene_Name 160832 1 hCG201364.3 A1BG alpha-1-B glycoprotein 223658 1 hCG201364.3 A1BG alpha-1-B glycoprotein 212988 102 hCG40040.3 ADAM10 ADAM metallopeptidase domain 10 133411 4185 hCG28232.2 ADAM11 ADAM metallopeptidase domain 11 110695 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 195222 8038 hCG40937.4 ADAM12 ADAM metallopeptidase domain 12 (meltrin alpha) 165344 8751 hCG20021.3 ADAM15 ADAM metallopeptidase domain 15 (metargidin) 189065 6868 null ADAM17 ADAM metallopeptidase domain 17 (tumor necrosis factor, alpha, converting enzyme) 108119 8728 hCG15398.4 ADAM19 ADAM metallopeptidase domain 19 (meltrin beta) 117763 8748 hCG20675.3 ADAM20 ADAM metallopeptidase domain 20 126448 8747 hCG1785634.2 ADAM21 ADAM metallopeptidase domain 21 208981 8747 hCG1785634.2|hCG2042897 ADAM21 ADAM metallopeptidase domain 21 180903 53616 hCG17212.4 ADAM22 ADAM metallopeptidase domain 22 177272 8745 hCG1811623.1 ADAM23 ADAM metallopeptidase domain 23 102384 10863 hCG1818505.1 ADAM28 ADAM metallopeptidase domain 28 119968 11086 hCG1786734.2 ADAM29 ADAM metallopeptidase domain 29 205542 11085 hCG1997196.1 ADAM30 ADAM metallopeptidase domain 30 148417 80332 hCG39255.4 ADAM33 ADAM metallopeptidase domain 33 140492 8756 hCG1789002.2 ADAM7 ADAM metallopeptidase domain 7 122603 101 hCG1816947.1 ADAM8 ADAM metallopeptidase domain 8 183965 8754 hCG1996391 ADAM9 ADAM metallopeptidase domain 9 (meltrin gamma) 129974 27299 hCG15447.3 ADAMDEC1 ADAM-like, -
Sleeping Beauty Transposon Mutagenesis Identifies Genes That
Sleeping Beauty transposon mutagenesis identifies PNAS PLUS genes that cooperate with mutant Smad4 in gastric cancer development Haruna Takedaa,b, Alistair G. Rustc,d, Jerrold M. Warda, Christopher Chin Kuan Yewa, Nancy A. Jenkinsa,e, and Neal G. Copelanda,e,1 aDivision of Genomics and Genetics, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673; bDepartment of Pathology, School of Medicine, Kanazawa Medical University, Ishikawa 920-0293, Japan; cExperimental Cancer Genetics, Wellcome Trust Sanger Institute, Cambridge CB10 1HH, United Kingdom; dTumour Profiling Unit, The Institute of Cancer Research, Chester Beatty Laboratories, London SW3 6JB, United Kingdom; and eCancer Research Program, Houston Methodist Research Institute, Houston, TX 77030 Contributed by Neal G. Copeland, February 27, 2016 (sent for review October 15, 2015; reviewed by Yoshiaki Ito and David A. Largaespada) Mutations in SMAD4 predispose to the development of gastroin- animal models that mimic human GC, researchers have infected testinal cancer, which is the third leading cause of cancer-related mice with H. pylori and then, treated them with carcinogens. They deaths. To identify genes driving gastric cancer (GC) development, have also used genetic engineering to develop a variety of trans- we performed a Sleeping Beauty (SB) transposon mutagenesis genic and KO mouse models of GC (10). Smad4 KO mice are one + − screen in the stomach of Smad4 / mutant mice. This screen iden- GC model that has been of particular interest to us (11, 12). tified 59 candidate GC trunk drivers and a much larger number of Heterozygous Smad4 KO mice develop polyps in the pyloric re- candidate GC progression genes. -
Comparative Transcriptomics Reveals Similarities and Differences
Seifert et al. BMC Cancer (2015) 15:952 DOI 10.1186/s12885-015-1939-9 RESEARCH ARTICLE Open Access Comparative transcriptomics reveals similarities and differences between astrocytoma grades Michael Seifert1,2,5*, Martin Garbe1, Betty Friedrich1,3, Michel Mittelbronn4 and Barbara Klink5,6,7 Abstract Background: Astrocytomas are the most common primary brain tumors distinguished into four histological grades. Molecular analyses of individual astrocytoma grades have revealed detailed insights into genetic, transcriptomic and epigenetic alterations. This provides an excellent basis to identify similarities and differences between astrocytoma grades. Methods: We utilized public omics data of all four astrocytoma grades focusing on pilocytic astrocytomas (PA I), diffuse astrocytomas (AS II), anaplastic astrocytomas (AS III) and glioblastomas (GBM IV) to identify similarities and differences using well-established bioinformatics and systems biology approaches. We further validated the expression and localization of Ang2 involved in angiogenesis using immunohistochemistry. Results: Our analyses show similarities and differences between astrocytoma grades at the level of individual genes, signaling pathways and regulatory networks. We identified many differentially expressed genes that were either exclusively observed in a specific astrocytoma grade or commonly affected in specific subsets of astrocytoma grades in comparison to normal brain. Further, the number of differentially expressed genes generally increased with the astrocytoma grade with one major exception. The cytokine receptor pathway showed nearly the same number of differentially expressed genes in PA I and GBM IV and was further characterized by a significant overlap of commonly altered genes and an exclusive enrichment of overexpressed cancer genes in GBM IV. Additional analyses revealed a strong exclusive overexpression of CX3CL1 (fractalkine) and its receptor CX3CR1 in PA I possibly contributing to the absence of invasive growth. -
Identification of Common Gene Networks Responsive To
Cancer Gene Therapy (2014) 21, 542–548 © 2014 Nature America, Inc. All rights reserved 0929-1903/14 www.nature.com/cgt ORIGINAL ARTICLE Identification of common gene networks responsive to radiotherapy in human cancer cells D-L Hou1, L Chen2, B Liu1, L-N Song1 and T Fang1 Identification of the genes that are differentially expressed between radiosensitive and radioresistant cancers by global gene analysis may help to elucidate the mechanisms underlying tumor radioresistance and improve the efficacy of radiotherapy. An integrated analysis was conducted using publicly available GEO datasets to detect differentially expressed genes (DEGs) between cancer cells exhibiting radioresistance and cancer cells exhibiting radiosensitivity. Gene Ontology (GO) enrichment analyses, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein–protein interaction (PPI) networks analysis were also performed. Five GEO datasets including 16 samples of radiosensitive cancers and radioresistant cancers were obtained. A total of 688 DEGs across these studies were identified, of which 374 were upregulated and 314 were downregulated in radioresistant cancer cell. The most significantly enriched GO terms were regulation of transcription, DNA-dependent (GO: 0006355, P = 7.00E-09) for biological processes, while those for molecular functions was protein binding (GO: 0005515, P = 1.01E-28), and those for cellular component was cytoplasm (GO: 0005737, P = 2.81E-26). The most significantly enriched pathway in our KEGG analysis was Pathways in cancer (P = 4.20E-07). PPI network analysis showed that IFIH1 (Degree = 33) was selected as the most significant hub protein. This integrated analysis may help to predict responses to radiotherapy and may also provide insights into the development of individualized therapies and novel therapeutic targets. -
Chd8 Mutation Leads to Autistic-Like Behaviors and Impaired Striatal Circuits
Chd8 Mutation Leads to Autistic-like Behaviors and Impaired Striatal Circuits The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Platt, Randall J.; Zhou, Yang; Slaymaker, Ian M.; Shetty, Ashwin S.; Weisbach, Niels R.; Kim, Jin-Ah; Sharma, Jitendra et al. “Chd8 Mutation Leads to Autistic-Like Behaviors and Impaired Striatal Circuits.” Cell Reports 19, no. 2 (April 2017): 335–350 © 2017 The Authors As Published http://dx.doi.org/10.1016/j.celrep.2017.03.052 Publisher Elsevier Version Final published version Citable link http://hdl.handle.net/1721.1/109830 Terms of Use Creative Commons Attribution-NonCommercial-NoDerivs License Detailed Terms http://creativecommons.org/licenses/by-nc-nd/4.0/ Article Chd8 Mutation Leads to Autistic-like Behaviors and Impaired Striatal Circuits Graphical Abstract Authors Randall J. Platt, Yang Zhou, Ian M. Slaymaker, ..., Gerald R. Crabtree, Guoping Feng, Feng Zhang Correspondence [email protected] (R.J.P.), [email protected] (F.Z.) Macrocephaly Gene dysregulation In Brief Platt et al. demonstrate that loss-of- +/– Chd8 function mutation of the high-confidence ASD-associated gene Chd8 results in behavioral and synaptic defects in mice. ASD-like behavior Synaptic dysfunction Highlights À d Chd8+/ mice display macrocephaly and ASD-like behaviors d Major insult to genome regulation and cellular processes in Chd8+/– mice d LOF Chd8 mutations cause synaptic dysfunction in the nucleus accumbens d NAc-specific perturbation of Chd8 in adult Cas9 mice recapitulates behavior Platt et al., 2017, Cell Reports 19, 335–350 April 11, 2017 ª 2017 The Authors. -
Mutations and Modeling of the Chromatin Remodeler CHD8 Define an Emerging Autism Etiology
REVIEW published: 17 December 2015 doi: 10.3389/fnins.2015.00477 Mutations and Modeling of the Chromatin Remodeler CHD8 Define an Emerging Autism Etiology Rebecca A. Barnard 1, Matthew B. Pomaville 1, 2 and Brian J. O’Roak 1* 1 Department of Molecular & Medical Genetics, Oregon Health & Science University, Portland, OR, USA, 2 Department of Biology, California State University, Fresno, CA, USA Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder with a strong but complex genetic component. Recent family based exome-sequencing strategies have identified recurrent de novo mutations at specific genes, providing strong evidence for ASD risk, but also highlighting the extreme genetic heterogeneity of the disorder. However, disruptions in these genes converge on key molecular pathways early in development. In particular, functional enrichment analyses have found that there is a bias toward genes involved in transcriptional regulation, such as chromatin modifiers. Here we review recent genetic, animal model, co-expression network, and functional genomics studies relating to the high confidence ASD risk gene, CHD8. CHD8, a chromatin remodeling factor, may serve as a “master regulator” of a common ASD etiology. Individuals with a CHD8 mutation show an ASD subtype that includes similar Edited by: physical characteristics, such as macrocephaly and prolonged GI problems including Gul Dolen, recurrent constipation. Similarly, animal models of CHD8 disruption exhibit enlarged Johns Hopkins University, USA head circumference and reduced gut motility phenotypes. Systems biology approaches Reviewed by: Jeffrey Varner, suggest CHD8 and other candidate ASD risk genes are enriched during mid-fetal Cornell University, USA development, which may represent a critical time window in ASD etiology. -
Genome-Wide Analysis of HPV Integration in Human Cancers Reveals Recurrent, Focal Genomic Instability
Downloaded from genome.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability Keiko Akagi*a,b,c, Jingfeng Li*a,b,c, Tatevik R. Broutianb,d, Hesed Padilla-Nashf, Weihong Xiaob,d, Bo Jiangb,d, James W. Roccog,h, Theodoros N. Teknosi, Bhavna Kumari, Danny Wangsaf, Dandan Hea,b,c, Thomas Riedf, David E. Symer** ŧ a,b,c,d,e, Maura L. Gillison** ŧ b,d aHuman Cancer Genetics Program and bViral Oncology Program, Departments of cMolecular Virology, Immunology and Medical Genetics, dInternal Medicine and eBioinformatics, The Ohio State University Comprehensive Cancer Center, Columbus OH; fCancer Genomics Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD; gCenter for Cancer Research and Department of Surgery, Massachusetts General Hospital, Boston, MA; hDepartment of Otolaryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA; iDepartment of Otolaryngology-Head and Neck Surgery, The Ohio State University Medical Center *These authors contributed equally to this work **These authors contributed equally to this work ŧ Corresponding authors David E. Symer, M.D., Ph.D. [email protected] Maura L. Gillison M.D., Ph.D. [email protected] Downloaded from genome.cshlp.org on October 2, 2021 - Published by Cold Spring Harbor Laboratory Press Akagi and Li et al SUMMARY Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. -
Histone 4 Lysine 20 Methylation: a Case for Neurodevelopmental Disease
biology Review Histone 4 Lysine 20 Methylation: A Case for Neurodevelopmental Disease Rochelle N. Wickramasekara and Holly A. F. Stessman * Department of Pharmacology, School of Medicine, Creighton University, Omaha, NE 68178, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-402-280-2255 Received: 28 December 2018; Accepted: 26 February 2019; Published: 3 March 2019 Abstract: Neurogenesis is an elegantly coordinated developmental process that must maintain a careful balance of proliferation and differentiation programs to be compatible with life. Due to the fine-tuning required for these processes, epigenetic mechanisms (e.g., DNA methylation and histone modifications) are employed, in addition to changes in mRNA transcription, to regulate gene expression. The purpose of this review is to highlight what we currently know about histone 4 lysine 20 (H4K20) methylation and its role in the developing brain. Utilizing publicly-available RNA-Sequencing data and published literature, we highlight the versatility of H4K20 methyl modifications in mediating diverse cellular events from gene silencing/chromatin compaction to DNA double-stranded break repair. From large-scale human DNA sequencing studies, we further propose that the lysine methyltransferase gene, KMT5B (OMIM: 610881), may fit into a category of epigenetic modifier genes that are critical for typical neurodevelopment, such as EHMT1 and ARID1B, which are associated with Kleefstra syndrome (OMIM: 610253) and Coffin-Siris syndrome (OMIM: 135900), respectively. Based on our current knowledge of the H4K20 methyl modification, we discuss emerging themes and interesting questions on how this histone modification, and particularly KMT5B expression, might impact neurodevelopment along with current challenges and potential avenues for future research.