Assinck Peggy, Duncan Greg J, Plemel Jason R, Lee Michael J, Stratton Jo A, Manesh Sohrab B, Liu Jie, Ramer Leanne M, Kang Shin H, Bergles Dwight E, Biernaskie Jeff, Tetzlaff Wolfram
International Collaboration on Repair Discoveries.
Graduate Program in Neuroscience.
J Neurosci. 2017 Sep 6;37(36):8635-8654. doi: 10.1523/JNEUROSCI.2409-16.2017. Epub 2017 Jul 31.
Spontaneous remyelination occurs after spinal cord injury (SCI), but the extent of myelin repair and identity of the cells responsible remain incompletely understood and contentious. We assessed the cellular origin of new myelin by fate mapping platelet-derived growth factor receptor α (PDGFRα), Olig2+, and P0+ cells following contusion SCI in mice. Oligodendrocyte precursor cells (OPCs; PDGFRα+) produced oligodendrocytes responsible for ensheathment of ∼30% of myelinated spinal axons at injury epicenter 3 months after SCI, demonstrating that these resident cells are a major contributor to oligodendrocyte regeneration. OPCs also produced the majority of myelinating Schwann cells in the injured spinal cord; invasion of peripheral myelinating (P0+) Schwann cells made only a limited contribution. These findings reveal that PDGFRα+ cells perform diverse roles in CNS repair, as multipotential progenitors that generate both classes of myelinating cells. This endogenous repair might be exploited as a therapeutic target for CNS trauma and disease. Spinal cord injury (SCI) leads to profound functional deficits, though substantial numbers of axons often survive. One possible explanation for these deficits is loss of myelin, creating conduction block at the site of injury. SCI leads to oligodendrocyte death and demyelination, and clinical trials have tested glial transplants to promote myelin repair. However, the degree and duration of myelin loss, and the extent and mechanisms of endogenous repair, have been contentious issues. Here, we use genetic fate mapping to demonstrate that spontaneous myelin repair by endogenous oligodendrocyte precursors is much more robust than previously recognized. These findings are relevant to many types of CNS pathology, raising the possibility that CNS precursors could be manipulated to repair myelin in lieu of glial transplantation.
脊髓损伤（SCI）后会发生自发的髓鞘再生，但髓鞘修复的程度以及负责修复的细胞身份仍未完全明确且存在争议。我们通过对小鼠挫伤性脊髓损伤后血小板衍生生长因子受体α（PDGFRα）、少突胶质细胞转录因子2阳性（Olig2+）和髓磷脂蛋白零阳性（P0+）细胞进行命运图谱分析，评估了新髓鞘的细胞起源。少突胶质前体细胞（OPCs；PDGFRα+）产生的少突胶质细胞在脊髓损伤3个月后负责损伤中心约30%有髓鞘包裹的脊髓轴突，这表明这些驻留细胞是少突胶质细胞再生的主要贡献者。OPCs还产生了损伤脊髓中大部分形成髓鞘的施万细胞；外周形成髓鞘的（P0+）施万细胞的侵入贡献有限。这些发现表明，PDGFRα+细胞在中枢神经系统修复中发挥着多种作用，作为产生两类形成髓鞘细胞的多能祖细胞。这种内源性修复可能被用作中枢神经系统创伤和疾病的治疗靶点。脊髓损伤（SCI）会导致严重的功能缺陷，尽管大量轴突通常能够存活。这些缺陷的一个可能解释是髓鞘丢失，在损伤部位造成传导阻滞。SCI会导致少突胶质细胞死亡和脱髓鞘，并且临床试验已经测试了胶质细胞移植以促进髓鞘修复。然而，髓鞘丢失的程度和持续时间，以及内源性修复的程度和机制，一直是有争议的问题。在这里，我们使用基因命运图谱来证明内源性少突胶质前体细胞自发的髓鞘修复比以前认为的要强大得多。这些发现与许多类型的中枢神经系统病理学相关，增加了可以操纵中枢神经系统前体细胞来修复髓鞘以替代胶质细胞移植的可能性。
