title: Fibroblast growth factor 4 is required but not sufficient for the astrocyte dedifferentiation.
abstract: Our recent studies demonstrated that mature astrocytes from spinal cord can be reprogrammed in vitro and in vivo to generate neural stem/progenitor cells (NSPCs) following treatment with conditioned medium collected from mechanically injured astrocytes. However, little is known regarding the molecular mechanisms underlying the reprogramming of astrocytes. Here, we show that fibroblast growth factor 4 (FGF4) exerts a critical role in synergistically converting astrocytes into NSPCs that can express multiple neural stem cell markers (nestin and CD133) and are capable of both self-renewal and differentiation into neurons and glia. Lack of FGF4 signals fails to elicit the dedifferentiation of astrocytes towards NSPCs, displaying a substantially lower efficiency in the reprogramming of astrocytes and a slower transition through fate-determined state. These astrocyte-derived NSPCs displayed relatively poor self-renewal and multipotency. More importantly, further investigation suggested that FGF4 is a key molecule necessary for activating PI3K/Akt/p21 signaling cascades, as well as their downstream effectors responsible for directing cell reprogramming towards NSPCs. Collectively, these findings provide a molecular basis for astrocyte dedifferentiation into NSPCs after central nervous system (CNS) injury and imply that FGF4 may be a clinically applicable molecule for in situ neural repair in the CNS disorders.
authors: Clinical Stem Cell Research Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200217, China.
authors: Guo-Dong
authors: GD
authors: Feng
authors: Bao-Rong
authors: BR
authors: He
authors: Fan
authors: F
authors: Lu
authors: Lin-Hong
authors: LH
authors: Liu
authors: Lingling
authors: L
authors: Zhang
authors: Bo
authors: B
authors: Chen
authors: Zu-Ping
authors: ZP
authors: He
authors: Ding-Jun
authors: DJ
authors: Hao
authors: Hao
authors: H
authors: Yang
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D054337:Cell Dedifferentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051519:Fibroblast Growth Factor 4 / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
chemical_list: C496447:Fgf4 protein, rat; D051519:Fibroblast Growth Factor 4