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TISSUE-SPECIFIC STEM CELLS

Adult Germ Line Stem Cells as a Source of Functional Neurons and Glia

^aInstitute of Reconstructive Neurobiology and
^bInstitute of Physiology 1, LIFE & BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany;
^cInstitute of Human Genetics, Georg-August-University of Göttingen, Göttingen, Germany;
^dInstitute of Genetics, International Centre for Life, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom

Key Words. Germ line • Adult stem cells • Pluripotency • Neural differentiation

Correspondence: Correspondence: Oliver Brüstle, M.D., Institute of Reconstructive Neurobiology, University of Bonn LIFE & BRAIN Center, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. Telephone: +49-228-6885-500; Fax: +49-228-6885-501; e-mail: brustle{at}uni-bonn.de

Received on February 19, 2008; accepted for publication on July 1, 2008.

First published online in STEM CELLS EXPRESS  July 17, 2008.

The derivation of autologous pluripotent cells has become a central goal in translational stem cell research. Although somatic cell nuclear transfer and transcription factor-based reprogramming enable the generation of pluripotent cells from adult tissue, both methodologies depend on complex epigenetic alterations. Recent data suggest that the adult germ line may represent an alternative and natural source of pluripotent stem cells. Multipotent adult germ line stem cells (maGSCs) with properties similar to those of embryonic stem cells have been derived from mouse spermatogonial stem cells. These cells exhibit extensive self-renewal, expression of pluripotency markers, and differentiation into derivatives of all three germ layers. Here we report the derivation of multipotent neural and glial precursors as well as adherently proliferating neural stem cells from maGSCs. Characterization of maGSC-derived neurons revealed segregation into GABAergic, glutamatergic, serotonergic, and tyrosine hydroxylase-positive phenotypes. On a functional level, maGSC-derived neurons generate spontaneously active functional networks, which use both glutamatergic and GABAergic synaptic transmission and engage in synchronized oscillatory activity. maGSC-derived oligodendrocytes undergo full maturation and ensheathe host axons in myelin-deficient tissue. Our data suggest that neural stem and precursor cells derived from maGSCs could provide a versatile and potentially autologous source of functional neurons and glia.

Disclosure of potential conflicts of interest is found at the end of this article.