Inserm, U 1127, F-75013, Paris, France.
CNRS, UMR 7225, F-75013, Paris, France.
Stem Cells. 2015 Jun;33(6):2011-24. doi: 10.1002/stem.1997. Epub 2015 Apr 21.
It has been proposed that the adult dorsal root ganglia (DRG) harbor neural stem/progenitor cells (NPCs) derived from the neural crest. However, the thorough characterization of their stemness and differentiation plasticity was not addressed. In this study, we investigated adult DRG-NPC stem cell properties overtime, and their fate when ectopically grafted in the central nervous system. We compared them in vitro and in vivo to the well-characterized adult spinal cord-NPCs derived from the same donors. Using micro-dissection and neurosphere cultures, we demonstrate that adult DRG-NPCs have quasi unlimited self-expansion capacities without compromising their tissue specific molecular signature. Moreover, they differentiate into multiple peripheral lineages in vitro. After transplantation, adult DRG-NPCs generate pericytes in the developing forebrain but remyelinating Schwann cells in response to spinal cord demyelination. In addition, we show that axonal and endothelial/astrocytic factors as well astrocytes regulate the fate of adult DRG-NPCs in culture. Although the adult DRG-NPC multipotency is restricted to the neural crest lineage, their dual responsiveness to developmental and lesion cues highlights their impressive adaptive and repair potentials making them valuable targets for regenerative medicine.
有人提出,成人背根神经节 (DRG) 中存在源自神经嵴的神经干细胞/祖细胞 (NPCs)。然而,其干性和分化可塑性的全面特征尚未得到解决。在这项研究中,我们研究了成年 DRG-NPC 干细胞特性随时间的变化,以及它们在外周神经系统异位移植时的命运。我们将它们在体外和体内与来自同一供体的、特征明确的成年脊髓 NPC 进行了比较。使用微解剖和神经球培养,我们证明成年 DRG-NPC 具有近乎无限的自我扩增能力,而不会损害其组织特异性分子特征。此外,它们在体外可分化为多种周围谱系。移植后,成年 DRG-NPC 在前脑发育中产生周细胞,但在脊髓脱髓鞘时产生髓鞘再生 Schwann 细胞。此外,我们还表明,轴突和血管内皮/星形胶质细胞因子以及星形胶质细胞调节成年 DRG-NPC 在培养中的命运。尽管成年 DRG-NPC 的多能性仅限于神经嵴谱系,但它们对发育和损伤线索的双重反应突出了其令人印象深刻的适应性和修复潜力,使它们成为再生医学的有价值的靶标。