Fibroblast Growth Factor 4 Is Required but not Sufficient for the Astrocyte Dedifferentiation
Fibroblast Growth Factor 4 Is Required but not Sufficient for the Astrocyte Dedifferentiation
复制标题
成纤维细胞生长因子 4 是星形胶质细胞去分化所必需的，但还不够
DOI：
10.1007/s12035-014-8649-1
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发表时间：
2014-12-01
影响因子：
5.1
通讯作者：
Yang, Hao
中科院分区：
文献类型：
--
作者：
Feng, Guo-Dong;He, Bao-Rong;Yang, Hao
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.
