Temporal Profiling of Astrocyte Precursors Reveals Parallel Roles forAsefduring Development and after Injury
| Autor: | Jeanne M. Manalo, Benjamin Deneen, Hyun Kyoung Lee, Chad J. Creighton, Yoshihiro Kawasaki, Stacey M. Glasgow, Carrie A. Mohila, Fengju Chen, Lesley S. Chaboub, Tetsu Akiyama, Chay T. Kuo |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Aging Spinal Cord Regeneration Cell type Time Factors Mice Transgenic Biology Blood–brain barrier Mice 03 medical and health sciences Astrocyte differentiation medicine Animals Guanine Nucleotide Exchange Factors Humans Gene Spinal Cord Injuries Research Articles Mice Knockout General Neuroscience White Matter Injury Cns function Spinal cord 030104 developmental biology medicine.anatomical_structure Astrocytes Female Neuroscience Rho Guanine Nucleotide Exchange Factors Astrocyte |
| Zdroj: | The Journal of Neuroscience. 36:11904-11917 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | 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 lackingAsefexhibited 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 ofAsef, highlight the parallels between astrocyte development and their reactive counterparts associated with injury.SIGNIFICANCE STATEMENTAstrocytes play a central role in CNS function and associated diseases. Yet the mechanisms that control their development remain poorly defined. Using the developing mouse spinal cord as a model system, we identify molecular changes that occur in developing astrocytes. These molecular signatures are strongly correlated with human astrocyte expression profiles and validation in mouse spinal cord identifies a host of new genes associated with the astrocyte lineage. These genes are present in reactive astrocytes in human white matter injury, and functional studies reveal that one of these genes,Asef, contributes to reactive astrocyte responses after injury. These studies identify distinct stages of astrocyte lineage development and highlight the parallels between astrocyte development and their reactive counterparts associated with injury. |
| Databáze: | OpenAIRE |
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