TY - JOUR AU - Laug, Dylan AU - Huang, Teng-Wei AU - Huerta, Navish A. Bosquez AU - Huang, Anna Yu-Szu AU - Sardar, Debosmita AU - Ortiz-Guzman, Joshua AU - Carlson, Jeffrey C. AU - Arenkiel, Benjamin R. AU - Kuo, Chay T. AU - Mohila, Carrie A. AU - Glasgow, Stacey M. AU - Lee, Hyun Kyoung AU - Deneen, Benjamin T1 - Nuclear factor I-A regulates diverse reactive astrocyte responses after CNS injury PY - 2019/10/01/ AB - Reactive astrocytes are associated with every form of neurological injury. Despite their ubiquity, the molecular mechanisms controlling their production and diverse functions remain poorly defined. Because many features of astrocyte development are recapitulated in reactive astrocytes, we investigated the role of nuclear factor I-A (NFIA), a key transcriptional regulator of astrocyte development whose contributions to reactive astrocytes remain undefined. Here, we show that NFIA is highly expressed in reactive astrocytes in human neurological injury and identify unique roles across distinct injury states and regions of the CNS. In the spinal cord, after white matter injury (WMI), NFIA-deficient astrocytes exhibit defects in blood-brain barrier remodeling, which are correlated with the suppression of timely remyelination. In the cortex, after ischemic stroke, NFIA is required for the production of reactive astrocytes from the subventricular zone (SVZ). Mechanistically, NFIA directly regulates the expression of thrombospondin 4 (Thbs4) in the SVZ, revealing a key transcriptional node regulating reactive astrogenesis. Together, these studies uncover critical roles for NFIA in reactive astrocytes and illustrate how region- and injury-specific factors dictate the spectrum of reactive astrocyte responses. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI127492 VL - 129 IS - 10 UR - https://doi.org/10.1172/JCI127492 SP - 4408 EP - 4418 PB - The American Society for Clinical Investigation ER -