The Dynamic Proteome of Oligodendrocyte Lineage Differentiation Features Planar Cell Polarity and Macroautophagy Pathways

Abstract Background Generation of oligodendrocytes is a sophisticated multistep process, the mechanistic underpinnings of which are not fully understood and demand further investigation. To systematically profile proteome dynamics during human embryonic stem cell differentiation into oligodendrocytes, we applied in-depth quantitative proteomics at different developmental stages and monitored changes in protein abundance using a multiplexed tandem mass tag-based proteomics approach. Findings Our proteome data provided a comprehensive protein expression profile that highlighted specific expression clusters based on the protein abundances over the course of human oligodendrocyte lineage differentiation. We identified the eminence of the planar cell polarity signalling and autophagy (particularly macroautophagy) in the progression of oligodendrocyte lineage differentiation—the cooperation of which is assisted by 106 and 77 proteins, respectively, that showed significant expression changes in this differentiation process. Furthermore, differentially expressed protein analysis of the proteome profile of oligodendrocyte lineage cells revealed 378 proteins that were specifically upregulated only in 1 differentiation stage. In addition, comparative pairwise analysis of differentiation stages demonstrated that abundances of 352 proteins differentially changed between consecutive differentiation time points. Conclusions Our study provides a comprehensive systematic proteomics profile of oligodendrocyte lineage cells that can serve as a resource for identifying novel biomarkers from these cells and for indicating numerous proteins that may contribute to regulating the development of myelinating oligodendrocytes and other cells of oligodendrocyte lineage. We showed the importance of planar cell polarity signalling in oligodendrocyte lineage differentiation and revealed the autophagy-related proteins that participate in oligodendrocyte lineage differentiation.

[1]  Maggie,et al.  To A∞ And Beyond , 2021, A Gentle Introduction to Homological Mirror Symmetry.

[2]  D. Henderson,et al.  The formation of paranodal spirals at the ends of CNS myelin sheaths requires the planar polarity protein Vangl2 , 2020, Glia.

[3]  D. Rubinsztein,et al.  Autophagy induction as a therapeutic strategy for neurodegenerative diseases. , 2019, Journal of molecular biology.

[4]  R. Fields,et al.  Autophagy in Myelinating Glia , 2019, The Journal of Neuroscience.

[5]  S. Whittemore,et al.  Autophagy is essential for oligodendrocyte differentiation, survival, and proper myelination , 2019, Glia.

[6]  M. Morris,et al.  Modeling Mammalian Commitment to the Neural Lineage Using Embryos and Embryonic Stem Cells , 2019, Front. Physiol..

[7]  M. Ramanathan,et al.  Epidemiology and treatment of multiple sclerosis in elderly populations , 2019, Nature Reviews Neurology.

[8]  A. Ferlini,et al.  Autophagy induction in atrophic muscle cells requires ULK1 activation by TRIM32 through unanchored K63-linked polyubiquitin chains , 2019, Science Advances.

[9]  T. Chao,et al.  Musashi-1 Enhances Glioblastoma Migration by Promoting ICAM1 Translation12345 , 2019, Neoplasia.

[10]  W. Carré,et al.  Targeted panel sequencing establishes the implication of planar cell polarity pathway and involves new candidate genes in neural tube defect disorders , 2019, Human Genetics.

[11]  P. Thomas,et al.  Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0) , 2019, Nature Protocols.

[12]  S. Graham,et al.  Amyloid β Induces Early Changes in the Ribosomal Machinery, Cytoskeletal Organization and Oxidative Phosphorylation in Retinal Photoreceptor Cells , 2019, Front. Mol. Neurosci..

[13]  S. Graham,et al.  Upregulation of Proteolytic Pathways and Altered Protein Biosynthesis Underlie Retinal Pathology in a Mouse Model of Alzheimer’s Disease , 2019, Molecular Neurobiology.

[14]  A. Shetty,et al.  Neural stem cell derived extracellular vesicles: Attributes and prospects for treating neurodegenerative disorders , 2018, EBioMedicine.

[15]  The UniProt Consortium,et al.  UniProt: a worldwide hub of protein knowledge , 2018, Nucleic Acids Res..

[16]  W. Talbot,et al.  The Lysosomal Transcription Factor TFEB Represses Myelination Downstream of the Rag-Ragulator Complex. , 2018, Developmental cell.

[17]  Xinyu Zhao,et al.  Regulatory discrimination of mRNAs by FMRP controls mouse adult neural stem cell differentiation , 2018, Proceedings of the National Academy of Sciences.

[18]  H. Fu,et al.  Oligodendrocytes Development and Wnt Signaling Pathway , 2018, International Journal of Human Anatomy.

[19]  R. Almeida.  The Rules of Attraction in Central Nervous System Myelination , 2018, Front. Cell. Neurosci..

[20]  P. Tesar,et al.  Rapid functional genetics of the oligodendrocyte lineage using pluripotent stem cells , 2018, Nature Communications.

[21]  Xuting Bian,et al.  Direct reprogramming of fibroblasts into neural stem cells by single non-neural progenitor transcription factor Ptf1a , 2018, Nature Communications.

[22]  D. Rubinsztein,et al.  Autophagy as a promoter of longevity: insights from model organisms , 2018, Nature Reviews Molecular Cell Biology.

[23]  M. Abu-Rub,et al.  Emerging Cellular and Molecular Strategies for Enhancing Central Nervous System (CNS) Remyelination , 2018, Brain sciences.

[24]  T. Ma,et al.  Dynamic Calcium Release From Endoplasmic Reticulum Mediated by Ryanodine Receptor 3 Is Crucial for Oligodendroglial Differentiation , 2018, Front. Mol. Neurosci..

[25]  Wei Zheng,et al.  Neural stem cells for disease modeling and evaluation of therapeutics for infantile (CLN1/PPT1) and late infantile (CLN2/TPP1) neuronal ceroid lipofuscinoses , 2018, Orphanet Journal of Rare Diseases.

[26]  M. van de Rijn,et al.  Vangl2/RhoA Signaling Pathway Regulates Stem Cell Self-Renewal Programs and Growth in Rhabdomyosarcoma. , 2018, Cell stem cell.

[27]  S. Hoerstrup,et al.  Induced pluripotent stem cells derived from human amnion in chemically defined conditions , 2018, Cell cycle.

[28]  M. Cieśla,et al.  Heme oxygenase‐1 affects generation and spontaneous cardiac differentiation of induced pluripotent stem cells , 2018, IUBMB life.

[29]  F. Lu,et al.  Autophagy in Stem Cell Biology: A Perspective on Stem Cell Self-Renewal and Differentiation , 2018, Stem cells international.

[30]  A. Maffei,et al.  Non-canonical Wnt signaling regulates neural stem cell quiescence during homeostasis and after demyelination , 2018, Nature Communications.

[31]  K. Nakashima,et al.  HMGB2 expression is associated with transition from a quiescent to an activated state of adult neural stem cells , 2018, Developmental dynamics : an official publication of the American Association of Anatomists.

[32]  Yi Ding,et al.  Exploring the Mechanisms of Electroacupuncture-Induced Analgesia through RNA Sequencing of the Periaqueductal Gray , 2017, International journal of molecular sciences.

[33]  R. Sun,et al.  Structural Differences between the Lignin-Carbohydrate Complexes (LCCs) from 2- and 24-Month-Old Bamboo (Neosinocalamus affinis) , 2017, International journal of molecular sciences.

[34]  E. Mazzon,et al.  Prolonged Expansion Induces Spontaneous Neural Progenitor Differentiation from Human Gingiva-Derived Mesenchymal Stem Cells. , 2017, Cellular reprogramming.

[35]  M. Kilberg,et al.  Asparagine synthetase: Function, structure, and role in disease , 2017, The Journal of Biological Chemistry.

[36]  Ziyun Jiang,et al.  Hydrophilic cell-derived extracellular matrix as a niche to promote adhesion and differentiation of neural progenitor cells , 2017 .

[37]  M. Barbacid,et al.  Cyclin‐Dependent Kinase 4 Regulates Adult Neural Stem Cell Proliferation and Differentiation in Response to Insulin , 2017, Stem cells.

[38]  M. Su,et al.  Missing Value Imputation Approach for Mass Spectrometry-based Metabolomics Data , 2017, bioRxiv.

[39]  Hendrik G. Stunnenberg,et al.  The interplay of epigenetic marks during stem cell differentiation and development , 2017, Nature Reviews Genetics.

[40]  Pengbo Zhang,et al.  Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells , 2017, Front. Cell. Neurosci..

[41]  E. Bézard,et al.  Insulin resistance and exendin-4 treatment for multiple system atrophy , 2017, Brain : a journal of neurology.

[42]  Daniel C. Factor,et al.  Modeling the Mutational and Phenotypic Landscapes of Pelizaeus-Merzbacher Disease with Human iPSC-Derived Oligodendrocytes. , 2017, American journal of human genetics.

[43]  C. Henderson,et al.  LINGO-1 Regulates Oligodendrocyte Differentiation through the Cytoplasmic Gelsolin Signaling Pathway , 2017, The Journal of Neuroscience.

[44]  John B. Wallingford,et al.  Planar cell polarity in development and disease , 2017, Nature Reviews Molecular Cell Biology.

[45]  P. Vora,et al.  pERK1/2 Peripheral Recruitment and Filopodia Protrusion Augment Oligodendrocyte Progenitor Cell Migration: Combined Effects of PDGF-A and Fibronectin , 2016, Cellular and Molecular Neurobiology.

[46]  Shaoping Ji,et al.  RNA-binding Protein Quaking Stabilizes Sirt2 mRNA during Oligodendroglial Differentiation* , 2017, The Journal of Biological Chemistry.

[47]  J. Karanicolas,et al.  Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets , 2017, Clinical Cancer Research.

[48]  M. Knobloch.  The Role of Lipid Metabolism for Neural Stem Cell Regulation , 2017, Brain plasticity.

[49]  Kwangsik Nho,et al.  Adult neurogenesis and neurodegenerative diseases: A systems biology perspective , 2017, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[50]  L. Weiner,et al.  The influence of retinoic acid on the human oligodendrocyte precursor cells by RNA-sequencing , 2016, Biochemistry and biophysics reports.

[51]  Amos Bairoch,et al.  The neXtProt knowledgebase on human proteins: 2017 update , 2016, Nucleic Acids Res..

[52]  Juan Antonio Vizcaíno,et al.  The ProteomeXchange consortium in 2017: supporting the cultural change in proteomics public data deposition , 2016, Nucleic Acids Res..

[53]  Wei Zhang,et al.  COL3A1 and SNAP91: novel glioblastoma markers with diagnostic and prognostic value , 2016, Oncotarget.

[54]  S. Lipton,et al.  Quantitative Analysis of Human Pluripotency and Neural Specification by In-Depth (Phospho)Proteomic Profiling , 2016, Stem cell reports.

[55]  Esra Bozgeyik,et al.  Gene expression profiles of autophagy-related genes in multiple sclerosis. , 2016, Gene.

[56]  J. Relvas,et al.  Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair , 2016, Front. Cell Dev. Biol..

[57]  Jens Hjerling-Leffler,et al.  Oligodendrocyte heterogeneity in the mouse juvenile and adult central nervous system , 2016, Science.

[58]  Andrew D. Rouillard,et al.  Enrichr: a comprehensive gene set enrichment analysis web server 2016 update , 2016, Nucleic Acids Res..

[59]  T. Graeber,et al.  Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor , 2016, Nature Communications.

[60]  A. Józkowicz,et al.  Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism , 2016, Cellular and Molecular Life Sciences.

[61]  V. Fossati,et al.  Epigenetic Modulation of Human Induced Pluripotent Stem Cell Differentiation to Oligodendrocytes , 2016, International journal of molecular sciences.

[62]  G. Smyth,et al.  ROBUST HYPERPARAMETER ESTIMATION PROTECTS AGAINST HYPERVARIABLE GENES AND IMPROVES POWER TO DETECT DIFFERENTIAL EXPRESSION. , 2016, The annals of applied statistics.

[63]  J. Chick,et al.  Induction of virulence factors in Giardia duodenalis independent of host attachment , 2016, Scientific Reports.

[64]  B. Liu,et al.  MAZ mediates the cross-talk between CT-1 and NOTCH1 signaling during gliogenesis , 2016, Scientific Reports.

[65]  B. Berninger,et al.  Mapping gene regulatory circuitry of Pax6 during neurogenesis , 2016, Cell Discovery.

[66]  S. Goldman,et al.  How to make an oligodendrocyte , 2015, Development.

[67]  Sergej Nowoshilow,et al.  Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration , 2015, eLife.

[68]  J. Rinn,et al.  A comparison of genetically matched cell lines reveals the equivalence of human iPSCs and ESCs , 2015, Nature Biotechnology.

[69]  D. Pleasure,et al.  Canonical Wnt signaling in the oligodendroglial lineage–puzzles remain , 2015, Glia.

[70]  J. Seong,et al.  Glutamine contributes to maintenance of mouse embryonic stem cell self-renewal through PKC-dependent downregulation of HDAC1 and DNMT1/3a , 2015, Cell cycle.

[71]  W. Le,et al.  Role of autophagy in the pathogenesis of multiple sclerosis , 2015, Neuroscience Bulletin.

[72]  A. Faissner,et al.  The extracellular matrix compartment of neural stem and glial progenitor cells , 2015, Glia.

[73]  J. Andersen.  Study of Ascl1 function in the neurogenic lineage of the adult mouse hippocampus , 2015 .

[74]  A. Diallo,et al.  Investigation of genes important in neurodevelopment disorders in adult human brain , 2015, Human Genetics.

[75]  Jennifer Tsialikas,et al.  LIN28: roles and regulation in development and beyond , 2015, Development.

[76]  V. Fossati,et al.  Generation and isolation of oligodendrocyte progenitor cells from human pluripotent stem cells , 2015, Nature Protocols.

[77]  T. Boczek,et al.  Regulation of GAP43/calmodulin complex formation via calcineurin-dependent mechanism in differentiated PC12 cells with altered PMCA isoforms composition , 2015, Molecular and Cellular Biochemistry.

[78]  S. Goldman,et al.  Glia Disease and Repair-Remyelination. , 2015, Cold Spring Harbor perspectives in biology.

[79]  Jian-Fu Chen,et al.  Lin28 promotes the proliferative capacity of neural progenitor cells in brain development , 2015, Development.

[80]  S. Goebbels,et al.  The Polarity Protein Scribble Regulates Myelination and Remyelination in the Central Nervous System , 2015, PLoS biology.

[81]  M. Małecki,et al.  Induced pluripotent stem cells as a model for diabetes investigation , 2015, Scientific Reports.

[82]  P. Gutin,et al.  Human embryonic stem cell-derived oligodendrocyte progenitors remyelinate the brain and rescue behavioral deficits following radiation. , 2015, Cell stem cell.

[83]  J. Liu,et al.  Effect of tumor necrosis factor-related apoptosis-inducing ligand on developing human oligodendrocytes in culture , 2014, Molecular Biology.

[84]  S. Lipton,et al.  Transcriptional profiling of MEF2-regulated genes in human neural progenitor cells derived from embryonic stem cells , 2014, Genomics data.

[85]  Robert Zweigerdt,et al.  Controlling Expansion and Cardiomyogenic Differentiation of Human Pluripotent Stem Cells in Scalable Suspension Culture , 2014, Stem cell reports.

[86]  C. Allis,et al.  Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells , 2014, Nature.

[87]  Roland Eils,et al.  circlize implements and enhances circular visualization in R , 2014, Bioinform..

[88]  Chao Zhao,et al.  The EIIIA domain from astrocyte‐derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination , 2014, Glia.

[89]  V. Fossati,et al.  Efficient Generation of Myelinating Oligodendrocytes from Primary Progressive Multiple Sclerosis Patients by Induced Pluripotent Stem Cells , 2014, Stem cell reports.

[90]  J. Paik,et al.  Metabolic circuits in neural stem cells , 2014, Cellular and Molecular Life Sciences.

[91]  Barbara Corneo,et al.  CORTECON: A Temporal Transcriptome Analysis of In Vitro Human Cerebral Cortex Development from Human Embryonic Stem Cells , 2014, Neuron.

[92]  Z. Dai,et al.  Stage-Specific Regulation of Oligodendrocyte Development by Wnt/β-Catenin Signaling , 2014, The Journal of Neuroscience.

[93]  Edward L. Huttlin,et al.  MultiNotch MS3 Enables Accurate, Sensitive, and Multiplexed Detection of Differential Expression across Cancer Cell Line Proteomes , 2014, Analytical chemistry.

[94]  A. Annenkov.  Receptor Tyrosine Kinase (RTK) Signalling in the Control of Neural Stem and Progenitor Cell (NSPC) Development , 2014, Molecular Neurobiology.

[95]  R. Lovell-Badge,et al.  Stem cell factor Sox2 and its close relative Sox3 have differentiation functions in oligodendrocytes , 2014, Development.

[96]  G. Walko,et al.  Stabilization of the dystroglycan complex in Cajal bands of myelinating Schwann cells through plectin‐mediated anchorage to vimentin filaments , 2013, Glia.

[97]  Chun-Teng Huang,et al.  SOX2–LIN28/let-7 pathway regulates proliferation and neurogenesis in neural precursors , 2013, Proceedings of the National Academy of Sciences.

[98]  I. Duncan,et al.  Autophagy Promotes Oligodendrocyte Survival and Function following Dysmyelination in a Long-Lived Myelin Mutant , 2013, The Journal of Neuroscience.

[99]  E. Chen,et al.  Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool , 2013, BMC Bioinformatics.

[100]  Daniel C. Factor,et al.  Transcription factor–mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells , 2013, Nature Biotechnology.

[101]  S. Tenzer,et al.  A critical role for the cholesterol‐associated proteolipids PLP and M6B in myelination of the central nervous system , 2013, Glia.

[102]  S. Villapol,et al.  TGF-β Superfamily Gene Expression and Induction of the Runx1 Transcription Factor in Adult Neurogenic Regions after Brain Injury , 2013, PloS one.

[103]  Danwei Huangfu,et al.  Human pluripotent stem cells: an emerging model in developmental biology , 2013, Development.

[104]  J. Pasquini,et al.  Neural and oligodendrocyte progenitor cells: transferrin effects on cell proliferation , 2013, ASN neuro.

[105]  Hua Cheng,et al.  Regulation of Neural Stem Cell Differentiation by Transcription Factors HNF4-1 and MAZ-1 , 2013, Molecular Neurobiology.

[106]  C. Antoniades,et al.  Wnt signaling in cardiovascular physiology , 2012, Trends in Endocrinology & Metabolism.

[107]  Pham Jt,et al.  Specification of neural cell fate and regulation of neural stem cell proliferation by microRNAs , 2012 .

[108]  Shuiliang Yu,et al.  Retinoic Acid Induces Neurogenesis by Activating Both Retinoic Acid Receptors (RARs) and Peroxisome Proliferator-activated Receptor β/δ (PPARβ/δ)* , 2012, The Journal of Biological Chemistry.

[109]  Xiaolong Yang,et al.  Pax6 Directly Down-Regulates Pcsk1n Expression Thereby Regulating PC1/3 Dependent Proinsulin Processing , 2012, PloS one.

[110]  Ryan W. Wilson,et al.  Identification of retinol binding protein 1 promoter hypermethylation in isocitrate dehydrogenase 1 and 2 mutant gliomas. , 2012, Journal of the National Cancer Institute.

[111]  B. Merrill.  Wnt pathway regulation of embryonic stem cell self-renewal. , 2012, Cold Spring Harbor perspectives in biology.

[112]  Chiu-Ying Peng,et al.  Exacerbation of oxidative stress-induced cell death and differentiation in induced pluripotent stem cells lacking heme oxygenase-1. , 2012, Stem cells and development.

[113]  Shaoping Ji,et al.  Sirt2 is a novel in vivo downstream target of Nkx2.2 and enhances oligodendroglial cell differentiation. , 2011, Journal of molecular cell biology.

[114]  Zhigang Xue,et al.  Dynamic expression of synemin isoforms in mouse embryonic stem cells and neural derivatives , 2011, BMC Cell Biology.

[115]  S. Sokol.  Maintaining embryonic stem cell pluripotency with Wnt signaling , 2011, Development.

[116]  Jean-Léon Thomas,et al.  A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells , 2011, Proceedings of the National Academy of Sciences.

[117]  Jennifer M. Bolin,et al.  Proteomic and phosphoproteomic comparison of human ES and iPS cells , 2011, Nature Methods.

[118]  Nandini A. Sahasrabuddhe,et al.  Quantitative temporal proteomic analysis of human embryonic stem cell differentiation into oligodendrocyte progenitor cells , 2011, Proteomics.

[119]  P. Scacheri,et al.  Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells , 2011, Nature Methods.

[120]  Helga Thorvaldsdóttir,et al.  Molecular signatures database (MSigDB) 3.0 , 2011, Bioinform..

[121]  Peter Bühlmann,et al.  MissForest - non-parametric missing value imputation for mixed-type data , 2011, Bioinform..

[122]  Chang-jie Chen,et al.  Differential gene expression in oligodendrocyte progenitor cells, oligodendrocytes and type II astrocytes. , 2011, The Tohoku journal of experimental medicine.

[123]  K. Nave,et al.  Lipid metabolism in myelinating glial cells: lessons from human inherited disorders and mouse models , 2011, Journal of Lipid Research.

[124]  Hanbo Chen,et al.  VennDiagram: a package for the generation of highly-customizable Venn and Euler diagrams in R , 2011, BMC Bioinformatics.

[125]  A. Rezza,et al.  The overexpression of the putative gut stem cell marker Musashi-1 induces tumorigenesis through Wnt and Notch activation , 2010, Journal of Cell Science.

[126]  C. ffrench-Constant,et al.  Regulatory Mechanisms that Mediate Tenascin C-Dependent Inhibition of Oligodendrocyte Precursor Differentiation , 2010, The Journal of Neuroscience.

[127]  N. Mizushima,et al.  Autophagy in mammalian development and differentiation , 2010, Nature Cell Biology.

[128]  S. Rangaraju,et al.  Rapamycin Activates Autophagy and Improves Myelination in Explant Cultures from Neuropathic Mice , 2010, The Journal of Neuroscience.

[129]  S. Gygi,et al.  Network organization of the human autophagy system , 2010, Nature.

[130]  H. Iwatsuki,et al.  Transient expression of keratin during neuronal development in the adult rabbit spinal ganglion , 2010, Anatomical science international.

[131]  J. Ovádi,et al.  Tubulin polymerization‐promoting protein (TPPP/p25) is critical for oligodendrocyte differentiation , 2010, Glia.

[132]  C. Redies,et al.  Cadherin-19 expression is restricted to myelin-forming cells in the chicken embryo , 2010, Neuroscience.

[133]  V. Yong,et al.  Fibronectin attenuates process outgrowth in oligodendrocytes by mislocalizing MMP-9 activity , 2009, Molecular and Cellular Neuroscience.

[134]  D. Rowitch,et al.  Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. , 2009, Genes & development.

[135]  N. Ishiguro,et al.  Soft Tissue Sarcomas of the Chest Wall , 2009, Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer.

[136]  S. Tenzer,et al.  Myelin Proteomics: Molecular Anatomy of an Insulating Sheath , 2009, Molecular Neurobiology.

[137]  M. Tomishima,et al.  Highly efficient neural conversion of human ES and iPS cells by dual inhibition of SMAD signaling , 2009, Nature Biotechnology.

[138]  G. Robertson,et al.  Elevated ATG5 expression in autoimmune demyelination and multiple sclerosis , 2009, Autophagy.

[139]  Ming Yi,et al.  bioDBnet: the biological database network , 2009, Bioinform..

[140]  Brad T. Sherman,et al.  Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists , 2008, Nucleic acids research.

[141]  Zhou-Feng Chen,et al.  Rest-Mediated Regulation of Extracellular Matrix Is Crucial for Neural Development , 2008, PloS one.

[142]  A. Toutain,et al.  Glutamine synthetase is essential for proliferation of fetal skin fibroblasts. , 2008, Archives of biochemistry and biophysics.

[143]  Mustafa Sahin,et al.  Response of a Neuronal Model of Tuberous Sclerosis to Mammalian Target of Rapamycin (mTOR) Inhibitors: Effects on mTORC1 and Akt Signaling Lead to Improved Survival and Function , 2008, The Journal of Neuroscience.

[144]  Guido Kroemer,et al.  Autophagy in the Pathogenesis of Disease , 2008, Cell.

[145]  J. Chan,et al.  Cdk5 regulates differentiation of oligodendrocyte precursor cells through the direct phosphorylation of paxillin , 2007, Journal of Cell Science.

[146]  V. Lakics,et al.  N‐WASP regulates extension of filopodia and processes by oligodendrocyte progenitors, oligodendrocytes, and Schwann cells—implications for axon ensheathment at myelination , 2007, Glia.

[147]  Yi Wei Zhang,et al.  Oligodendrocyte progenitor cells derived from human embryonic stem cells express neurotrophic factors. , 2006, Stem cells and development.

[148]  A. Butt,et al.  Neurotransmitter‐mediated calcium signalling in oligodendrocyte physiology and pathology , 2006, Glia.

[149]  Yue Feng,et al.  QKI binds MAP1B mRNA and enhances MAP1B expression during oligodendrocyte development. , 2006, Molecular biology of the cell.

[150]  Dinender K. Singla,et al.  wnt3a but not wnt11 supports self-renewal of embryonic stem cells. , 2006, Biochemical and biophysical research communications.

[151]  J. Benjamins,et al.  Nitric oxide synthase expression and nitric oxide toxicity in oligodendrocytes. , 2006, Antioxidants & redox signaling.

[152]  H. Baharvand,et al.  Generation of new human embryonic stem cell lines with diploid and triploid karyotypes , 2006, Development, growth & differentiation.

[153]  Pablo Tamayo,et al.  Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[154]  S. Mcconnell,et al.  Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap , 2005, Development.

[155]  K. Anderson,et al.  Tissue morphogenesis and vascular stability require the Frem2 protein, product of the mouse myelencephalic blebs gene. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[156]  A. Csillag,et al.  SCL, GATA-2 and Lmo2 expression in neurogenesis , 2005, International Journal of Developmental Neuroscience.

[157]  K. Boheler,et al.  Somatic Stem Cell Marker Prominin‐1/CD133 Is Expressed in Embryonic Stem Cell–Derived Progenitors , 2005, Stem cells.

[158]  A. Howell,et al.  A putative human breast stem cell population is enriched for steroid receptor-positive cells. , 2005, Developmental biology.

[159]  M. Richards,et al.  The Transcriptome Profile of Human Embryonic Stem Cells as Defined by SAGE , 2004, Stem cells.

[160]  Arnold J. Levine,et al.  Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[161]  Jeffrey D. Axelrod,et al.  A Second Canon , 2003 .

[162]  Y. Ron,et al.  Regulation of gene expression in experimental autoimmune encephalomyelitis indicates early neuronal dysfunction. , 2003, Brain : a journal of neurology.

[163]  C. Hsu,et al.  Restricted expression of LUZP in neural lineage cells: a study in embryonic stem cells. , 2001, Journal of biomedical science.

[164]  J. Honnorat,et al.  Isolation and Expression Pattern of Human Unc-33-Like Phosphoprotein 6/Collapsin Response Mediator Protein 5 (Ulip6/CRMP5): Coexistence with Ulip2/CRMP2 in Sema3A- Sensitive Oligodendrocytes , 2001, The Journal of Neuroscience.

[165]  N. Baumann,et al.  Biology of oligodendrocyte and myelin in the mammalian central nervous system. , 2001, Physiological reviews.

[166]  B. Soliven.  Calcium signalling in cells of oligodendroglial lineage , 2001, Microscopy research and technique.

[167]  B. Angst,et al.  COMMENTARY The cadherin superfamily: diversity in form and function , 2022 .

[168]  L. Haak,et al.  Mitochondria in myelinating cells: calcium signaling in oligodendrocyte precursor cells. , 2000, Cell calcium.

[169]  J. Honnorat,et al.  Differential Expression of Collapsin Response Mediator Proteins (CRMP/ULIP) in Subsets of Oligodendrocytes in the Postnatal Rodent Brain , 2000, Molecular and Cellular Neuroscience.

[170]  J. Fawcett,et al.  N-Cadherin Influences Migration of Oligodendrocytes on Astrocyte Monolayers , 2000, Molecular and Cellular Neuroscience.

[171]  H. Okano,et al.  Musashi1: An Evolutionally Conserved Marker for CNS Progenitor Cells Including Neural Stem Cells , 2000, Developmental Neuroscience.

[172]  Peter E. Braun,et al.  Overexpression of 2′,3′-Cyclic Nucleotide 3′-Phosphodiesterase in Transgenic Mice Alters Oligodendrocyte Development and Produces Aberrant Myelination , 1996, Molecular and Cellular Neuroscience.

[173]  J. Baudier,et al.  Expression of neuromodulin (GAP‐43) and its regulation by basic fibroblast growth factor during the differentiation of O‐2A progenitor cells , 1993, Journal of neuroscience research.

[174]  G. Piras,et al.  A role for TGF-beta in oligodendrocyte differentiation , 1993, The Journal of cell biology.

[175]  R. Reynolds,et al.  Down‐regulation of GAP‐43 During Oligodendrocyte Development and Lack of Expression by Astrocytes In Vivo: Implications for Macroglial Differentiation , 1991, The European journal of neuroscience.

[176]  D. Storm,et al.  Neuromodulin (GAP43): a neuronal protein kinase C substrate is also present in 0-2A glial cell lineage. Characterization of neuromodulin in secondary cultures of oligodendrocytes and comparison with the neuronal antigen , 1990, The Journal of cell biology.

[177]  D. Wessel,et al.  A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids. , 1984, Analytical biochemistry.

[178]  Michael P. Windham,et al.  Cluster Validity for the Fuzzy c-Means Clustering Algorithrm , 1982, IEEE Transactions on Pattern Analysis and Machine Intelligence.

[179]  Dana Pascovici,et al.  TMT One-Stop Shop: From Reliable Sample Preparation to Computational Analysis Platform. , 2017, Methods in molecular biology.

[180]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[181]  Chao Zhao,et al.  Fibronectin aggregation in multiple sclerosis lesions impairs remyelination. , 2013, Brain : a journal of neurology.

[182]  J. Pham,et al.  Specification of neural cell fate and regulation of neural stem cell proliferation by microRNAs. , 2012, American journal of stem cells.

[183]  K. Mace,et al.  Progenitor Cells , 2012, Methods in Molecular Biology.

[184]  T. Boczek,et al.  Gene expression pattern in PC12 cells with reduced PMCA2 or PMCA3 isoform: selective up-regulation of calmodulin and neuromodulin , 2011, Molecular and Cellular Biochemistry.

[185]  Brad T. Sherman,et al.  Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources , 2008, Nature Protocols.

[186]  H. Okano,et al.  Expression of RNA-binding protein Musashi in hair follicle development and hair cycle progression. , 2006, The American journal of pathology.

[187]  P. Greengard,et al.  Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor , 2004, Nature Medicine.

[188]  Cathy H. Wu,et al.  UniProt: the Universal Protein knowledgebase , 2004, Nucleic Acids Res..

[189]  M. Gnegy,et al.  Calmodulin in neurotransmitter and hormone action. , 1993, Annual review of pharmacology and toxicology.

[190]  N. Kruger,et al.  The bradford method for protein quantitation. , 1988, Methods in molecular biology.

[191]  H. S. Tager,et al.  Peptide hormones. , 1974, Annual review of biochemistry.

[192]  L. Wolpert.  Developmental Biology , 1968, Nature.