Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cord

Neeta Roy, Takahiro Nakano, H. Michael Keyoung, Martha Windrem, William K. Rashbaum, M. Lita Alonso, Jian Kang, Weiguo Peng, Melissa K. Carpenter, Jane Lin, Maiken Nedergaard, Steven A. Goldman

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)297-305
Number of pages9
JournalNature Biotechnology
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Fingerprint

Telomerase
Neurons
Spinal Cord
Stem Cells
Mental Competency
Cell Aging
Motor Neurons
Interneurons
Fibroblast Growth Factor 2
Green Fluorescent Proteins
Heterografts
Neuroglia
Neurology
Fibroblasts
Carcinogenesis
Central Nervous System
Rats
Brain
Proteins
human TERT protein

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering

Cite this

Roy, N., Nakano, T., Keyoung, H. M., Windrem, M., Rashbaum, W. K., Alonso, M. L., ... Goldman, S. A. (2004). Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cord. Nature Biotechnology, 22(3), 297-305. https://doi.org/10.1038/nbt944

Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cord. / Roy, Neeta; Nakano, Takahiro; Keyoung, H. Michael; Windrem, Martha; Rashbaum, William K.; Alonso, M. Lita; Kang, Jian; Peng, Weiguo; Carpenter, Melissa K.; Lin, Jane; Nedergaard, Maiken; Goldman, Steven A.

In: Nature Biotechnology, Vol. 22, No. 3, 01.03.2004, p. 297-305.

Research output: Contribution to journalArticle

Roy, N, Nakano, T, Keyoung, HM, Windrem, M, Rashbaum, WK, Alonso, ML, Kang, J, Peng, W, Carpenter, MK, Lin, J, Nedergaard, M & Goldman, SA 2004, 'Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cord', Nature Biotechnology, vol. 22, no. 3, pp. 297-305. https://doi.org/10.1038/nbt944
Roy, Neeta ; Nakano, Takahiro ; Keyoung, H. Michael ; Windrem, Martha ; Rashbaum, William K. ; Alonso, M. Lita ; Kang, Jian ; Peng, Weiguo ; Carpenter, Melissa K. ; Lin, Jane ; Nedergaard, Maiken ; Goldman, Steven A. / Telomerase immortalization of neuronally restricted progenitor cells derived from the human fetal spinal cord. In: Nature Biotechnology. 2004 ; Vol. 22, No. 3. pp. 297-305.
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