title: V-myc immortalizes human neural stem cells in the absence of pluripotency-associated traits.
abstract: A better understanding of the molecular mechanisms governing stem cell self-renewal will foster the use of different types of stem cells in disease modeling and cell therapy strategies. Immortalization, understood as the capacity for indefinite expansion, is needed for the generation of any cell line. In the case of v-myc immortalized multipotent human Neural Stem Cells (hNSCs), we hypothesized that v-myc immortalization could induce a more de-differentiated state in v-myc hNSC lines. To test this, we investigated the expression of surface, biochemical and genetic markers of stemness and pluripotency in v-myc immortalized and control hNSCs (primary precursors, that is, neurospheres) and compared these two cell types to human Embryonic Stem Cells (hESCs) and fibroblasts. Using a Hierarchical Clustering method and a Principal Component Analysis (PCA), the v-myc hNSCs associated with their counterparts hNSCs (in the absence of v-myc) and displayed a differential expression pattern when compared to hESCs. Moreover, the expression analysis of pluripotency markers suggested no evidence supporting a reprogramming-like process despite the increment in telomerase expression. In conclusion, v-myc expression in hNSC lines ensures self-renewal through the activation of some genes involved in the maintenance of stem cell properties in multipotent cells but does not alter the expression of key pluripotency-associated genes.
authors.affiliation: Department of Molecular Biology and Center of Molecular Biology "Severo Ochoa" (CBMSO), Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas (UAM-CSIC), Campus UAM Cantoblanco, Madrid, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Pino-Barrio
authors.affiliation: Department of Molecular Biology and Center of Molecular Biology "Severo Ochoa" (CBMSO), Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas (UAM-CSIC), Campus UAM Cantoblanco, Madrid, Spain.
authors.forename: Elisa
authors.initials: E
authors.lastname: García-García
authors.affiliation: Josep Carreras Leukemia Research Institute and Cell Therapy Program, Facultat de Medicina, University of Barcelona, Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Menéndez
authors.affiliation: Department of Molecular Biology and Center of Molecular Biology "Severo Ochoa" (CBMSO), Universidad Autónoma de Madrid-Consejo Superior de Investigaciones Científicas (UAM-CSIC), Campus UAM Cantoblanco, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Martínez-Serrano
mesh_terms: D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D016000:Cluster Analysis; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D039902:Multipotent Stem Cells / Q000166:cytology / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology / Q000502:physiology*; D016274:Oncogene Protein p55(v-myc) / Q000378:metabolism*; D025341:Principal Component Analysis
chemical_list: D005819:Genetic Markers; D016274:Oncogene Protein p55(v-myc)