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Doctor of Philosophy (PHD)
Date of Defense
First Committee Member
Jae K. Lee
Second Committee Member
Nagi G. Ayad
Third Committee Member
Fourth Committee Member
NG2 cells, also known as oligodendrocyte progenitor cells (OPCs), are tiled throughout the adult central nervous system (CNS) and proliferate and differentiate into oligodendrocytes throughout life. After spinal cord injury (SCI), many oligodendrocytes are lost, and promoting oligodendrocyte differentiation is an appealing target to promote functional recovery after SCI. However, in addition to differentiating into oligodendrocytes, NG2 cells proliferate in the glial scar and contribute to axon regeneration failure. NG2 cells are committed to the oligodendrocyte lineage in adult mice. However, in other models of CNS injury, NG2 cells gain the capacity to differentiate into astrocytes. The astroglial fate of NG2 cells after SCI is currently unknown and is important to investigate because astrocytes are major contributors to the glial scar. To trace the fate of NG2 cells after SCI, I used NG2-CreER mice bred to tdTomato, which serves as a Cre reporter. I found that in addition to increasing their proliferation and differentiation into oligodendrocytes after SCI, NG2 cells gain the capacity to differentiate into astrocytes in the glial scar. Mechanisms that underlie these fate changes are not well understood. Since cytokine ligands for the signal transducer and activator of transcription 3 (STAT3) pathway are upregulated after SCI, and have been implicated in NG2 cell and astrocyte fate, I hypothesized that the transcription factor STAT3 might to an important mediator of NG2 cell fate after SCI. To address the role of STAT3 in NG2 cells after SCI, I used tamoxifen inducible NG2 cell specific deletions of either STAT3 or its suppressor, suppressor of cytokine signaling 3 (SOCS3). I have identified STAT3 as an important regulator of efficient oligodendrogenesis after SCI. Surprisingly, I found that SOCS3 deletion led to increased proliferation of NG2 cells via a STAT3 independent mechanism. I also found that neither STAT3 nor SOCS3 affected astrogliogenesis from NG2 cells after SCI. Altogether these data suggest that STAT3 and SOCS3 are important regulators of NG2 cell proliferation and differentiation after SCI. Understanding mechanisms that mediate NG2 cell proliferation and differentiation in the glial scar is essential since NG2 cells are important players in axon regeneration failure after SCI. My data reveal insight into the role of cytokine signaling in both oligodendrogenesis and proliferation of NG2 cells, and could be used to alter glial scar formation or promote remyelination after SCI.
Spinal Cord Injury; Glial Scar; Oligodendrocytes; Cytokines
Hackett, Amber R., "The Role of NG2 Cells after Contusive Spinal Cord Injury" (2016). Open Access Dissertations. 1767.