Adult germ line stem cells as a source of functional neurons and glia.
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.
Glaser
Tamara
T
Institute of Reconstructive Neurobiology, University of Bonn LIFE & BRAIN Center, University of Bonn and Hertie Foundation, Bonn, Germany.
Opitz
Thoralf
T
Kischlat
Thomas
T
Konang
Rachel
R
Sasse
Philipp
P
Fleischmann
Bernd K
BK
Engel
Wolfgang
W
Nayernia
Karim
K
Brüstle
Oliver
O
D053687:Adult Stem Cells / Q000166:cytology* / Q000502:physiology; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005854:Germ Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D051379:Mice; D009457:Neuroglia / Q000166:cytology* / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology
D000943:Antigens, Differentiation