Nature Biotechnology
22, 297 - 305 (2004)
Published online: 15 February 2004; | doi:10.1038/nbt944
Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cordNeeta S Roy1, Takahiro Nakano1, H Michael Keyoung1, Martha Windrem1, 6, William K Rashbaum2, M Lita Alonso3, Jian Kang4, Weiguo Peng4, Melissa K Carpenter5, Jane Lin4, Maiken Nedergaard4, 6
& Steven A Goldman1, 61
Departments of Neurology and Neuroscience, Cornell University Medical Center, New York, New York
10021, USA. 2
Departments of Obstetrics and Gynecology, Cornell University Medical Center, New York, New York
10021, USA. 3
Department of Pathology, Cornell University Medical Center, New York, New York
10021, USA. 4
Department of Cell Biology, New York Medical College, Valhalla, New York
10595, USA. 5
Geron Corp., Menlo Park, California, 94025, USA. 6
University of Rochester Medical Center, 601 Elmwood Ave., Rochester, New York
14642, USA.
Correspondence should be addressed to Steven A Goldman steven_goldman@urmc.rochester.eduLineage-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 survived >168 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.
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