STAT3 and SOCS3 regulate NG2 cell proliferation and differentiation after contusive spinal cord injury

• Published in: Neurobiology of disease Vol. 89; pp. 10 - 22
• Main Authors: Hackett, Amber R, Lee, Do-Hun, Dawood, Abdul, Rodriguez, Mario, Funk, Lucy, Tsoulfas, Pantelis, Lee, Jae K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-05-2016; Elsevier
• Subjects: Animals; Astrocytes; Astrocytes - physiology; Cell Count; Cell Differentiation; Cell Proliferation; Female; Glial scar; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurology; Oligodendrocyte progenitor cells; Oligodendrocytes; Oligodendroglia - metabolism; Oligodendroglia - physiology; Spinal Cord Injuries - physiopathology; STAT3 Transcription Factor - genetics; STAT3 Transcription Factor - physiology; Stem Cells - physiology; Suppressor of Cytokine Signaling 3 Protein - genetics; Suppressor of Cytokine Signaling 3 Protein - physiology; CNTF; OPC; Oligodendrocyte progenitor cell; Oligodendrocyte progenitor cells; Glial scar; Ciliary neurotrophic factor; Spinal cord injury; SOCS3; 5-Ethynyl-2′-deoxyuridine; TUNEL; Signal transducer and activator of transcription 3; Oligodendrocytes; NG2; Janus kinase; Neural glial antigen 2; 4′,6-Diamidino-2-phenylindole; Astrocytes; Glial fibrillary acidic protein; Leukemia inhibitory factor; STAT3; LIF; Suppressor of cytokine signaling 3; DAPI; GFAP; Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling; JAK; EdU; CSPG; SCI; Chondroitin sulfate proteoglycan
• ISSN: 0969-9961; 1095-953X
• DOI: 10.1016/j.nbd.2016.01.017

Abstract NG2 cells, also known as oligodendrocyte progenitors or polydendrocytes, are a major component of the glial scar that forms after spinal cord injury. NG2 cells react to injury by proliferating around the lesion site and differentiating into oligodendrocytes and astrocytes, but the molecular mechanism is poorly understood. In this study, we tested the role of the transcription factor STAT3, and its suppressor SOCS3, in NG2 cell proliferation and differentiation after spinal cord injury. Using knockout mice in which STAT3 or SOCS3 are genetically deleted specifically in NG2 cells, we found that deletion of STAT3 led to a reduction in oligodendrogenesis, while deletion of SOCS3 led to enhanced proliferation of NG2 cells within the glial scar after spinal cord injury. Additionally, STAT3 and SOCS3 were not required for astrogliogenesis from NG2 cells after spinal cord injury. Interestingly, genetic deletion of STAT3 and SOCS3 did not have opposing effects, suggesting that SOCS3 may have targets other than the STAT3 pathway in NG2 cells after spinal cord injury. Altogether, our data show that both STAT3 and SOCS3 play important, yet unexpected, roles in NG2 cell proliferation and differentiation after spinal cord injury.