Stem cell-derived neural stem/progenitor cell supporting factor is an autocrine/paracrine survival factor for adult neural stem/progenitor cells.
Recent evidence suggests that adult neural stem/progenitor cells (ANSCs) secrete autocrine/paracrine factors and that these intrinsic factors are involved in the maintenance of adult neurogenesis. We identified a novel secretory molecule, stem cell-derived neural stem/progenitor cell supporting factor (SDNSF), from adult hippocampal neural stem/progenitor cells by using the signal sequence trap method. The expression of SDNSF in adult central nervous system was localized to hippocampus including dentate gyrus, where the neurogenesis persists throughout life. In induced neurogenesis status seen in ischemically treated hippocampus, the expression of SDNSF was up-regulated. As functional aspects, SDNSF protein provided a dose-dependent survival effect for ANSC following basic fibroblast growth factor 2 (FGF-2) withdrawal. ANSCs treated by SDNSF also retain self-renewal potential and multipotency in the absence of FGF-2. However, SDNSF did not have mitogenic activity, nor was it a cofactor that promoted the mitogenic effects of FGF-2. These data suggested an important role of SDNSF as an autocrine/paracrine factor in maintaining stem cell potential and lifelong neurogenesis in adult central nervous system.
Toda
Hiroki
H
Department of Medical Chemistry, Kyoto University Graduate School of Medicine, Yoshida Konoe-cho, Sakyoku, Kyoto 606-8501, Japan.
Tsuji
Masayuki
M
Nakano
Ichiro
I
Kobuke
Kazuhiro
K
Hayashi
Takeshi
T
Kasahara
Hironori
H
Takahashi
Jun
J
Mizoguchi
Akira
A
Houtani
Takeshi
T
Sugimoto
Tetsuo
T
Hashimoto
Nobuo
N
Palmer
Theo D
TD
Honjo
Tasuku
T
Tashiro
Kei
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002545:Brain Ischemia / Q000503:physiopathology; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D019089:Stem Cell Factor / Q000235:genetics / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D014162:Transfection; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000502:physiology*
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D017931:DNA Primers; D018076:DNA, Complementary; C475146:MCFD2 protein, human; C515308:MCFD2 protein, mouse; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D033921:Vesicular Transport Proteins