Journal
JOURNAL OF NEUROSCIENCE
Volume 36, Issue 47, Pages 11904-11917Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1658-16.2016
Keywords
astrocyte precursors; blood-brain barrier; reactive astrocytes; white matter injury
Categories
Funding
- Sontag Foundation
- National Multiple Sclerosis Society [RG-1501-02756]
- Cancer Prevention Research Institute of Texas [RP510334, RP160192, RP101499]
- National Institutes of Health [NS071153, P30 AI036211, P30 CA125123, S10 RR024574]
- Cytometry and Cell Sorting Core at Baylor College of Medicine
- Intellectual and Developmental Disabilities Research Center grant from the Eunice Kennedy Shriver National Institute of Child Health & Human Development [1U54 HD083092]
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Lineage development is a stepwise process, governed by stage-specific regulatory factors and associated markers. Astrocytes are one of the principle cell types in the CNS and the stages associated with their development remain very poorly defined. To identify these stages, we performed gene-expression profiling on astrocyte precursor populations in the spinal cord, identifying distinct patterns of gene induction during their development that are strongly correlated with human astrocytes. Validation studies identified a new cohort of astrocyte-associated genes during development and demonstrated their expression in reactive astrocytes in human white matter injury (WMI). Functional studies on one of these genes revealed that mice lacking Asef exhibited impaired astrocyte differentiation during development and repair after WMI, coupled with compromised blood-brain barrier integrity in the adult CNS. These studies have identified distinct stages of astrocyte lineage development associated with human WMI and, together with our functional analysis of Asef, highlight the parallels between astrocyte development and their reactive counterparts associated with injury.
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