| Studying central nervous system (CNS) homeostasis and pathology requires a fundamental understanding of astrocyte biology. Astrocytes have many roles ranging from regulating the extracellular environment to responding to CNS injuries. A multitude of molecular regulators, such as microRNAs (miRNAs), govern this plasticity. In this study, we focus on miRNA-21 and elucidate its roles in astrocyte biology.;In the context of spinal cord injury (SCI), we found that miR-21 is increased around the injury site and is expressed by astrocytes. Astrocytes respond to SCI with an initial phase of hypertrophy, which has beneficial effects. This is followed by astrocytic hyperplasia and glial scar formation. To study miR-21's role in astrocytes in vivo, we generated transgenic mice that over-express miR-21 or inhibit its function in a conditional manner. By modulating miR-21 in astrocytes, we showed that it contributes to the astrocytic transition between the two phases where blocking miR-21 function sustains hypertrophy. Moreover, this creates a permissive lesion environment, allowing for increased axons within the glial scar. We also determined that an increase in miR-21 occurs after traumatic brain injury (TBI), and that astrocytes are a source of miR-21, suggesting a conversed response by miR-21. However, the same effect in the astrocytic response was not detected.;miR-21 is known for its role in cancer and cancer stem cells. Given the similarities between cancer stem cells and neural/progenitor stem cells (NPSCs), we examined the role of miR-21 NPSCs. We found that the adult subventricular zone (SVZ), a neurogenic region in the brain and a source of NPSCs, expresses low levels of miR-21. NPSCs isolated from the adult SVZ also express miR-21. We determined that miR-21 does not have a significant role in NPSC proliferation under pro-growth conditions. However, in differentiating conditions, miR-21 maintains cell division and prevents cell death.;In summary, we describe the generation of novel tools to study miR-21 function in vivo and in vitro. By using these tools, we identify previously unknown functions of miR-21 in the astrocytic response to CNS injury and differentiation. |
