title: Human GPM6A is associated with differentiation and neuronal migration of neurons derived from human embryonic stem cells.
abstract: Glycoprotein M6A (GPM6A) is known as a transmembrane protein and an abundant cell surface protein on neurons in the central nervous system (CNS). However, the function of GPM6A in the differentiation of neurons derived from human embryonic stem (ES) cells is unknown. To investigate the function of GPM6A in neural differentiation, we generated human ES cell lines with overexpressed (B2h-oeM6A) or suppressed (B2h-shM6A) human GPM6A. Real-time polymerase chain reaction (PCR) showed that overexpression of GPM6A markedly increased the expression of neuroectodermal-associated genes (OTX1, Lmx1b, En1, Pax2, Sox2, and Wnt1), and the number of neural stem cells (NSCs) derived from B2h-oeM6A cells compared to control vector transfected human ES cells (B2h-Mock1). Our results show an increase in the number of differentiated neuronal cells (cholinergic, catecholaminergic, and GABAergic neurons) from NSCs derived from B2h-oeM6A cells. On the other hand, suppression of human GPM6A expression using a short hairpin RNA (shRNA) in human ES cells led to a decrease in both the expression of neuroectodermal-associated genes and the number of NSCs derived from B2h-shM6A cells. In addition, our results show a decrease in the number of differentiated neuronal cells from NSCs in B2h-shM6A cells compared to control vector transfected human ES cells (B2h-shNSP1). Moreover, overexpression or suppression of human GPM6A in human ES cells led to an increase or decrease, respectively, of neuronal migration. Hence, our findings suggest that expression level of GPM6A is, directly or indirectly, associated with the differentiation and neuronal migration of neurons derived from undifferentiated human ES cells.
authors.affiliation: Advanced Medical Research Laboratory, Mitsubishi Tanabe Pharma Corporation, Osaka, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Michibata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Okuno
authors.forename: Nae
authors.initials: N
authors.lastname: Konishi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Kyono
authors.forename: Koji
authors.initials: K
authors.lastname: Wakimoto
authors.forename: Kan
authors.initials: K
authors.lastname: Aoki
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kondo
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Takata
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Takashi
authors.initials: T
authors.lastname: Taniguchi
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*
chemical_list: C484158:GPM6A protein, human; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins