Nuclear factor I-A regulates diverse reactive astrocyte responses after CNS injury
| Autor: | Navish A. Bosquez Huerta, Joshua Ortiz-Guzman, Carrie A. Mohila, Benjamin Deneen, Teng-Wei Huang, Jeffrey C. Carlson, Hyun Kyoung Lee, Dylan Laug, Debosmita Sardar, Chay T. Kuo, Anna Yu-Szu Huang, Benjamin R. Arenkiel, Stacey M. Glasgow |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Adult Central Nervous System Multiple Sclerosis Subventricular zone Biology 03 medical and health sciences Mice 0302 clinical medicine Thrombospondin 4 Transcriptional regulation medicine Animals Humans Remyelination education Mice Knockout education.field_of_study Nuclear factor I Cell Differentiation General Medicine Cortex (botany) Stroke NFI Transcription Factors Oligodendroglia 030104 developmental biology medicine.anatomical_structure NFIA Blood-Brain Barrier 030220 oncology & carcinogenesis Astrocytes Thrombospondins Neuroscience Astrocyte Research Article |
| Zdroj: | The Journal of clinical investigation. 129(10) |
| ISSN: | 1558-8238 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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