title: lncRNA Functional Networks in Oligodendrocytes Reveal Stage-Specific Myelination Control by an lncOL1/Suz12 Complex in the CNS.
abstract: Long noncoding RNAs (lncRNAs) are emerging as important regulators of cellular functions, but their roles in oligodendrocyte myelination remain undefined. Through de novo transcriptome reconstruction, we establish dynamic expression profiles of lncRNAs at different stages of oligodendrocyte development and uncover a cohort of stage-specific oligodendrocyte-restricted lncRNAs, including a conserved chromatin-associated lncOL1. Co-expression network analyses further define the association of distinct oligodendrocyte-expressing lncRNA clusters with protein-coding genes and predict lncRNA functions in oligodendrocyte myelination. Overexpression of lncOL1 promotes precocious oligodendrocyte differentiation in the developing brain, whereas genetic inactivation of lncOL1 causes defects in CNS myelination and remyelination following injury. Functional analyses illustrate that lncOL1 interacts with Suz12, a component of polycomb repressive complex 2, to promote oligodendrocyte maturation, in part, through Suz12-mediated repression of a differentiation inhibitory network that maintains the precursor state. Together, our findings reveal a key lncRNA epigenetic circuitry through interaction with chromatin-modifying complexes in control of CNS myelination and myelin repair.
authors.affiliation: Divisions of Experimental Hematology and Cancer Biology & Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Integrative Biology Graduate Training Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Danyang
authors.initials: D
authors.lastname: He
authors.affiliation: Divisions of Experimental Hematology and Cancer Biology & Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Zhejiang Province Key Laboratory of Anti-cancer Drug Research, Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital of Fudan University, 201102 Shanghai, China.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Divisions of Experimental Hematology and Cancer Biology & Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Yaqi
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Divisions of Experimental Hematology and Cancer Biology & Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Chuntao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Divisions of Experimental Hematology and Cancer Biology & Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, 201102 Shanghai, China.
authors.forename: Lingli
authors.initials: L
authors.lastname: Xu
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Yinhuai
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Yueh-Chiang
authors.initials: YC
authors.lastname: Hu
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital of Fudan University, 201102 Shanghai, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Divisions of Experimental Hematology and Cancer Biology & Developmental Biology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA; Integrative Biology Graduate Training Program, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Key Laboratory of Birth Defects, Children's Hospital of Fudan University, 201102 Shanghai, China. Electronic address: richard.lu@cchmc.org.
authors.forename: Q Richard
authors.initials: QR
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000196:embryology*; D002454:Cell Differentiation / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D007150:Immunohistochemistry; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction; D058468:Receptors, Ionotropic Glutamate / Q000235:genetics*
chemical_list: D029721:Drosophila Proteins; C000621447:IR75b protein, Drosophila; D062085:RNA, Long Noncoding; D058468:Receptors, Ionotropic Glutamate; C494163:Suz12 protein, mouse; D063151:Polycomb Repressive Complex 2
keywords: EZH2; OPC; chromatin remodeling; functional genomics; long noncoding RNA; myelination; neural precursors; oligodendrocyte differentiation; polycomb repressive complex; remyelination