Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cord
| Autor: | Jane Lin, Takahiro Nakano, Jian Kang, Weiguo Peng, Melissa K. Carpenter, M. Lita Alonso, Neeta S. Roy, H. Michael Keyoung, Martha S. Windrem, Steven A. Goldman, William K. Rashbaum |
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| Rok vydání: | 2003 |
| Předmět: |
Telomerase
Cell Survival Biomedical Engineering Cell Culture Techniques Retroviridae Proteins Bioengineering Biology Applied Microbiology and Biotechnology Cell Line medicine Humans Progenitor cell Neurons Fetus Cell immortalization Neuronal Plasticity Tissue Engineering Stem Cells Cell Differentiation Spinal cord Cell biology DNA-Binding Proteins medicine.anatomical_structure Genetic Enhancement nervous system Spinal Cord embryonic structures Human fetal Immunology Molecular Medicine Neuron Nervous System Diseases Cell Division Biotechnology Stem Cell Transplantation |
| Zdroj: | Nature biotechnology. 22(3) |
| ISSN: | 1087-0156 |
| Popis: | Lineage-restricted progenitors of the central nervous system (CNS) are not readily expandable because their mitotic competence is limited. Here we used retroviral overexpression of human telomerase reverse transcriptase (hTERT) to immortalize progenitors from human fetal spinal cord. The hTERT-immortalized cells divided in basic fibroblast growth factor (bFGF) expressed high telomerase activity, and gave rise to phenotypically restricted subpopulations of either glia or neurons. The latter included a prototypic line, hSC11V-TERT, that gave rise only to neurons. These included both chx10(+) interneurons and Islet1(+)/Hb9(+)/ChAT(+) motor neurons; the latter were recognized by green fluorescent protein (GFP) driven by the Hb9 enhancer. The neurons were postmitotic and achieved electrophysiologic competence. Upon xenograft to both fetal rat brain and injured adult spinal cord, they matured as neurons and survived for 6 months, with no evident tumorigenesis. The cells have survived168 doublings in vitro, with karyotypic normalcy and without replicative senescence. hTERT overexpression thus permits the generation of progenitor lines able to give rise to phenotypically restricted neurons. |
| Databáze: | OpenAIRE |
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