論文紹介著者

Raye Zhan（博士課程 3年）
GCOE　RA
Department of Anatomy

第一著者名・掲載雑誌・号・掲載年月

Fadi J Najm／ADVANCE ONLINE PUBLICATION/NATURE MOTHEDS/Published online 25 September 2011

文献の英文表記：著者名・論文の表題・雑誌名・巻・号・ページ・発行年（西暦）

Fadi J Najm, Anita Zaremba, Andrew V Caprariello, Shreya Nayak, Eric C Freundt, Peter C Scacheri, Robert H Miller & Paul J Tesar. Rapid and robust generation of functional oligodendrocyte progenitor cells from epiblast stem cells. ADVANCE ONLINE PUBLICATION/NATURE MOTHEDS/Published online 25 September 2011

論文解説

Background

The myelin sheath around the axon acts like an electrical insulator for the effective conduction of action potentials along nerve axon. Loss of myelin impacts millions of people by causing impairment in sensation, movement, cognition, or other functions depending on which nerves are involved. Scientists believe that OPCs (Oligodendrocyte precursor cells) that retain the functional capabilities of response to signals and generation of myelinogenic oligodendrocytes are a sought-after target for demyelinating diseases※1. Current strategies often generate a mixture of uncharacterized neural precursors, not OPCs. Therefore, this study aimed to establish new methodologies to produce homogeneous functional OPCs.

Results

First, EpiSCs(the mouse epiblast stem cells)※2 were treated with molecules to direct them to become neuroectodermal cells. These cells then organized into structures called neural rosettes※3.To produce OPCs, the neural rosettes are then treated with a defined set of signaling proteins previously known to be important for generation of OPCs in the developing spinal cord. At the first stage, the neural rosettes gave rise to presumptive OPCs that expressed Olig2 or Nkx2.2. After this 5 day protocol, presumptive OPCs rapidly developed to nearly homogeneous population of cells exhibiting a typical bipolar morphology and expressing transcription factors and cell surface markers of OPCs. These EpiSCs-derived OPCs could be expanded for at least 8 passages, yielding previously unobtainable numbers of pure OPCs. In the T3 differentiate medium without both PDGF-AA and FGF2, EpiSCs-derived OPCs differentiated exclusively into O4⁺ oligodendrocyte with multiprocessed morphology within 4 days. The functional and myelinogenic properties of EpiSCs-derived OPCs were tested by both on the lab bench and in diseased mouse models, showed the OPCs specifically differentiated into MBP⁺※4 cells and restored normal myelin within days, demonstrating their potential use in therapeutic transplants.

Summary

Taken together, these results demonstrate that mouse EpiSCs efficiently provide a pure population of myelinogenic oligodendrocytes and offer a solid framework for the ability to produce analogous human cells for use in the clinic. Furthermore, this developmental system created a platform for discovering modulators of oligodendrocyte differentiation, myelination and drug screening.

用語解説

• ※1　 Demyelinating diseases
  the diseases of the nervous system in which the myelin sheath of neurons is damaged
• ※2　 Epiblast stem cells
  Epiblast stem cells (EpiSCs) which are derived from E5.5 or E6.5 mouse epiblasts, also express Oct4, Nanog, and Sox2 and exhibit features of pluripotency
• ※3　 Neural rosettes
  a distinct group of early-stage neural stem cells that can form more types of neural cells than typical neural stem cells
• ※4　 MBP
  Myelin Basic Protein, the major constituent of the CNS myelin synthesized by oligodendrocytes and Schwann cells