Kim Jaesang, Lo Liching, Dormand Emma, Anderson David J
Howard Hughes Medical Institute, Division of Biology 216-76, California Institute of Technology, Pasadena, California 91125, USA.
Neuron. 2003 Apr 10;38(1):17-31. doi: 10.1016/s0896-6273(03)00163-6.
The mechanisms that establish and maintain the multipotency of stem cells are poorly understood. In neural crest stem cells (NCSCs), the HMG-box factor SOX10 preserves not only glial, but surprisingly, also neuronal potential from extinction by lineage commitment signals. The latter function is reflected in the requirement of SOX10 in vivo for induction of MASH1 and PHOX2B, two neurogenic transcription factors. Simultaneously, SOX10 inhibits or delays overt neuronal differentiation, both in vitro and in vivo. However, this activity requires a higher Sox10 gene dosage than does the maintenance of neurogenic potential. The opponent functions of SOX10 to maintain neural lineage potentials, while simultaneously serving to inhibit or delay neuronal differentiation, suggest that it functions in stem or progenitor cell maintenance, in addition to its established role in peripheral gliogenesis.
目前人们对建立和维持干细胞多能性的机制了解甚少。在神经嵴干细胞(NCSCs)中,HMG盒因子SOX10不仅能维持神经胶质细胞的潜能,令人惊讶的是,它还能防止神经元潜能因谱系定向信号而丧失。后一种功能体现在体内SOX10对诱导两种神经源性转录因子MASH1和PHOX2B的必要性上。同时,SOX10在体外和体内均能抑制或延迟明显的神经元分化。然而,与维持神经源性潜能相比,这种活性需要更高的Sox10基因剂量。SOX10在维持神经谱系潜能的同时,还能抑制或延迟神经元分化,这表明它除了在周围神经胶质细胞生成中已确立的作用外,还在干细胞或祖细胞维持中发挥作用。