title: Early phenotypic asymmetry of sister oligodendrocyte progenitor cells after mitosis and its modulation by aging and extrinsic factors.
abstract: Oligodendrocyte progenitor cells (OPCs) persist in the adult central nervous system and guarantee oligodendrocyte turnover throughout life. It remains obscure how OPCs avoid exhaustion during adulthood. Similar to stem cells, OPCs could self-maintain by undergoing asymmetric divisions generating a mixed progeny either keeping a progenitor phenotype or proceeding to differentiation. To address this issue, we examined the distribution of stage-specific markers in sister OPCs during mitosis and later after cell birth, and assessed its correlation with distinct short-term fates. In both the adult and juvenile cerebral cortex a fraction of dividing OPCs gives rise to sister cells with diverse immunophenotypic profiles and short-term behaviors. Such heterogeneity appears as cells exit cytokinesis, but does not derive from the asymmetric segregation of molecules such as NG2 or PDGFRa expressed in the mother cell. Rather, rapid downregulation of OPC markers and upregulation of molecules associated with lineage progression contributes to generate early sister OPC asymmetry. Analyses during aging and upon exposure to physiological (i.e., increased motor activity) and pathological (i.e., trauma or demyelination) stimuli showed that both intrinsic and environmental factors contribute to determine the fraction of symmetric and asymmetric OPC pairs and the phenotype of the OPC progeny as soon as cells exit mitosis.
authors.affiliation: Department of Neuroscience, Neuroscience Institute Cavalieri Ottolenghi (NICO), Università degli Studi di Torino, Regione Gonzole, 10-10043, Orbassano (Turin), Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Boda
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Maria
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rosa
authors.forename: Verdon
authors.initials: V
authors.lastname: Taylor
authors.forename: Maria P
authors.initials: MP
authors.lastname: Abbracchio
authors.forename: Annalisa
authors.initials: A
authors.lastname: Buffo
mesh_terms: D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001973:Bromodeoxyuridine; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology; D005786:Gene Expression Regulation / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008938:Mitosis / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000502:physiology*; D011509:Proteoglycans / Q000235:genetics / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D011509:Proteoglycans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D012097:Repressor Proteins; D000099216:Chondroitin Sulfate Proteoglycan 4; C489685:Hes5 protein, mouse
keywords: NG2 cells; asymmetry; division; maturation