Stem Cell-derived Neural Stem/Progenitor Cell Supporting Factor Is an Autocrine/Paracrine Survival Factor for Adult Neural Stem/Progenitor Cells

Hiroki Toda,Masayuki Tsuji,Ichiro Nakano,Kazuhiro Kobuke,Takeshi Hayashi,Hironori Kasahara,Jun Takahashi,Akira Mizoguchi,Takeshi Houtani,Tetsuo Sugimoto,Nobuo Hashimoto,Theo D Palmer,Tasuku Honjo,Kei Tashiro

doi:10.1074/jbc.m305342200

Abstract

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.

Highlights

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
ANSC conditioned medium is known to provide both trophic and mitogenic support for ANSCs, and previous analysis of the ANSC conditioned medium led to the characterization of glycosylated cystatin C as a cofactor for fibroblast growth factor 2 (FGF-2) [15]
By analyzing roles of IGF-1 in epidermal growth factor (EGF)-dependent ANSCs, IGF-1 was identified as a cofactor of EGF [20]

Summary

Introduction

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. RNA Analysis and SDNSF cDNA Cloning—To isolate novel secretory or membrane proteins from neural stem cells, cDNA library was constructed from cultured ANSCs. Poly(A)ϩ RNA was extracted from ANSCs with TRIzol reagent (Invitrogen) and Oligotex-dT30 Super (Roche Applied Science).

Results

Conclusion