[Biological characteristics and functions of NG2-glia].

NG2-glia are a major type of glial cells that are widely distributed in the central nervous system (CNS). Under physiological conditions, they mainly differentiate into oligodendrocytes and contribute to the myelination of axons, so they are generally called oligodendrocyte progenitor cells. Emerging evidence suggests that NG2-glia not only act as the precursors of oligodendrocytes but also possess many other biological properties and functions. For example, NG2-glia can form synapse with neurons and participate in energy metabolism and immune regulation. Under pathological conditions, NG2-glia can also differentiate into astrocytes, Schwann cells and even neurons, which are involved in CNS injury and repair. Therefore, a deeper understanding of the biological characteristics and functions of NG2-glia under physiological and pathological conditions will be helpful for the treatment of CNS injury and disease. This article reviews the recent advances in the biological characteristics and functions of NG2-glia.

[Astrocytes as therapeutic targets after spinal cord injury].

Spinal cord injury (SCI) is a challenging medical problem in the field of neurology, showing high incidence rate, disability rate, treatment cost and low-aged trend. Despite the clinical application of drug intervention, surgical treatment and modern rehabilitation training, no ideal curative effect has been achieved. Therefore, future study is necessary to clarify detailed pathological mechanism of SCI and identify the potential target cells for therapeutic intervention. In the central nervous system (CNS), astrocytes are the most abundant and widely distributed glial cells which play multiple key roles in maintaining homeostasis of the CNS in physiological and pathological conditions. Increasing evidence indicates that astrocytes are ideal therapeutic target cells for SCI. Here, we review current knowledge of the roles of astrocytes in the pathological reaction after SCI, astroglial transplantation and astrocyte reprogramming.

[Glial cells function as neural stem cells and progenitor cells].

Glial cells, including astrocytes, oligodendrocyte progenitor cells (OPCs), NG2-glia, etc, are broadly distributed throughout the central nervous system (CNS). Also, it has been well known that glial cells play multi-roles in physiological and pathological processes in the CNS, such as maintaining homeostasis, providing neurotrophins for neurons and regulating neural signal transmission. Recently, increasing evidence showed that glial cells may also function as neural stem/progenitor cells and contribute to adult neurogenesis or neuroregeneration. In pathological conditions, for instance, astrocytes and OPCs could be activated to proliferate and differentiate. When cultured in vitro, they could form neurospheres which possess the ability to differentiate into astrocytes, oligodendrocytes and neurons. Additionally, forced expression of exogenous genes in astrocytes and NG2-glia can successfully reprogram them into neurons, which may also be suggestive of their stem/progenitor cell features. Here, we review current knowledge of the stem cell-like properties of glial cells, including what types of glial cells can function as stem/progenitor cells, how they can acquire the stem/progenitor potential and what progenies can be produced. These insights may foster a better understanding of glial cell biology and function in physiological or pathological processes in the CNS and lead to the idea of using the stem/progenitor-like glial cells as endogenous cell source for neural repair.

[Structural, mechanistic and functional insights into topoisomerase II].

Topoisomerases are nuclear enzymes that regulate the overwinding or underwinding of DNA helix during replication, transcription, recombination, repair, and chromatin remodeling. These enzymes perform topological transformations by providing a transient DNA break, through which the unique problems of DNA entanglement that occur owing to unwinding and rewinding of the DNA helix can be resolved. In mammals, topoisomerases are classified into two types, type I topoisomerase (Top1) and type II topoisomerase (Top2), depending on the number of strands cut in one round of action. Top1 induces single-strand breaks in DNA, and Top2 induces double-strand breaks. In cells from vertebrate species, there are two forms of Top2, designated alpha and beta. Top2α is involved in the cellular proliferation and pluripotency, while Top2ß plays key roles in neurodevelopment. In this review, we cover recent advances in structural, mechanistic and functional insights into Top2.

Slit-2 repels the migration of olfactory ensheathing cells by triggering Ca2+-dependent cofilin activation and RhoA inhibition.

Olfactory ensheathing cells (OECs) migrate from the olfactory epithelium towards the olfactory bulb during development. However, the guidance mechanism for OEC migration remains a mystery. Here we show that migrating OECs expressed the receptor of the repulsive guidance factor Slit-2. A gradient of Slit-2 in front of cultured OECs first caused the collapse of the leading front, then the reversal of cell migration. These Slit-2 effects depended on the Ca(2+) release from internal stores through inositol (1,4,5)-triphosphate receptor channels. Interestingly, in response to Slit-2 stimulation, collapse of the leading front required the activation of the F-actin severing protein cofilin in a Ca(2+)-dependent manner, whereas the subsequent reversal of the soma migration depended on the reversal of RhoA activity across the cell. Finally, the Slit-2-induced repulsion of cell migration was fully mimicked by co-application of inhibitors of F-actin polymerization and RhoA kinase. Our findings revealed Slit-2 as a repulsive guidance factor for OEC migration and an unexpected link between Ca(2+) and cofilin signaling during Slit-2-triggered repulsion.

Migratory properties of cultured olfactory ensheathing cells by single-cell migration assay.

Olfactory ensheathing cells (OECs) are a unique type of glial cells that have axonal growth-promoting properties. OEC transplantation has emerged as a promising experimental therapy of axonal injuries and demyelinating diseases. However, some fundamental cellular properties of OECs remain unclear. In this study, we found that the distinct OEC subpopulations exhibited different migratory properties based on time-lapse imaging of single isolated cells, possibly due to their different cytoskeletal organizations. Moreover, OEC subpopulations displayed different attractive migratory responses to a gradient of lysophosphatidic acid (LPA) in single-cell migration assays. Finally, we found that OEC subpopulations transformed into each other spontaneously. Together, these results demonstrate, for the first time to our knowledge, that distinct OEC subpopulations display different migratory properties in vitro and provide new evidence to support the notion of OECs as a single cell type with malleable functional phenotypes.