RT Journal Article
SR Electronic
T1 Generation of primitive neural stem cells from human fibroblasts using a defined set of factors
JF Biology Open
JO Biology Open
FD Company of Biologists
SP 1595
OP 1607
DO 10.1242/bio.013151
VO 4
IS 11
A1 Miura, Takumi
A1 Sugawara, Tohru
A1 Fukuda, Atsushi
A1 Tamoto, Ryo
A1 Kawasaki, Tomoyuki
A1 Umezawa, Akihiro
A1 Akutsu, Hidenori
YR 2015
UL http://bio.biologists.org/content/4/11/1595.abstract
AB In mice, leukemia inhibitory factor (LIF)-dependent primitive neural stem cells (NSCs) have a higher neurogenic potential than bFGF-dependent definitive NSCs. Therefore, expandable primitive NSCs are required for research and for the development of therapeutic strategies for neurological diseases. There is a dearth of suitable techniques for the generation of human long-term expandable primitive NSCs. Here, we have described a method for the conversion of human fibroblasts to LIF-dependent primitive NSCs using a strategy based on techniques for the generation of induced pluripotent stem cells (iPSCs). These LIF-dependent induced NSCs (LD-iNSCs) can be expanded for >100 passages. Long-term cultured LD-iNSCs demonstrated multipotent neural differentiation potential and could generate motor neurons and dopaminergic neurons, as well as astrocytes and oligodendrocytes, indicating a high level of plasticity. Furthermore, LD-iNSCs easily reverted to human iPSCs, indicating that LD-iNSCs are in an intermediate iPSC state. This method may facilitate the generation of patient-specific human neurons for studies and treatment of neurodegenerative diseases.