Generation of functional neurons and glia from multipotent adult mouse germ-line stem cells

Recently, we reported the successful establishment of multipotent adult germ-line stem cells (maGSCs) from cultured adult mouse spermatogonial stem cells. Similar to embryonic stem cells, maGSCs are able to self-renew and differentiate into derivatives of all three germ layers. These properties make maGSCs a potential cell source for the treatment of neural degenerative diseases. In this study, we describe the generation of maGSC-derived proliferating neural precursor cells using growth factor-mediated neural lineage induction. The neural precursors were positive for nestin and Sox1 and could be continuously expanded. Upon further differentiation, they formed functional neurons and glial cells, as demonstrated by expression of lineage-restricted genes and proteins and by electrophysiological properties. Characterization of maGSC-derived neurons revealed the generation of specific subtypes, including GABAergic, glutamatergic, serotonergic, and dopaminergic neurons. Electrophysiological analysis revealed passive and active membrane properties and postsynaptic currents, indicating their functional maturation. Functional networks formed at later stages of differentiation, as evidenced by synaptic transmission of spontaneous neuronal activity. In conclusion, our data demonstrate that maGSCs may be used as a new stem cell source for basic research and biomedical applications.