scholarly journals γ–Secretase controls the specification of astrocytes from oligodendrocyte precursor cells via Stat3

2019 ◽  
Author(s):  
Jinxing Hou ◽  
Huiru Bi ◽  
Gang Zou ◽  
Zhuoyang Ye ◽  
Jing Zhao ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Postnatal Development ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Signal Transducer ◽  
Brain Functions ◽  
Mechanistic Analysis ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor

AbstractOligodendrocytes (OLs) and astrocytes play critical roles in a variety of brain functions. OL precursor cells (OPCs) are known to give rise to OLs as well as astrocytes. However, little is known about the mechanism by which OPCs determine their specification choice for OLs versus astrocytes in the central nervous system (CNS). Here we show that genetic inhibition of γ-secretase in OPCs reduces OL differentiation but enhances astrocyte specification. Mechanistic analysis reveals that inhibition of γ-secretase results in decreased levels of Hes1, and that Hes1 down-regulates the expression of signal transducer and activator of transcription3 (Stat3) via binding to specific regions of its promoter. We demonstrate that conditional inactivation of Stat3 in OL lineages restores the number of astrocytes in γ-secretase mutant mice. In summary, this study identifies a key mechanism which controls OPC’s specification choice for OL versus astrocyte during postnatal development. This γ-secretase-dependent machinery may be essential for the CNS to maintain the population balance between OLs and astrocytes.

scholarly journals Olig genes are upregulated in oligodendrocyte precursor cells in the injured central nervous system

2013 ◽  
Vol 74 (1) ◽  
pp. 1-7
Author(s):  
Ken Iseki ◽  
Seita Hagino ◽  
Tetsuji Mori ◽  
Yuxiang Zhang ◽  
Nobuko Sakai ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Precursor Cells ◽  
Oligodendrocyte Precursor Cells ◽  
Oligodendrocyte Precursor

scholarly journals A Matter of State: Diversity in Oligodendrocyte Lineage Cells

2021 ◽  
pp. 107385842098720
Author(s):  
Yasmine Kamen ◽  
Helena Pivonkova ◽  
Kimberley A. Evans ◽  
Ragnhildur T. Káradóttir
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Adult Brain ◽  
Developmental Origins ◽  
Oligodendrocyte Precursor Cells ◽  
Homogeneous Population ◽  
Physiological Properties ◽  
The Central Nervous System ◽  
Oligodendrocyte Precursor ◽  
Transcriptome Response

Oligodendrocyte precursor cells (OPCs) give rise to oligodendrocytes which myelinate axons in the central nervous system. Although classically thought to be a homogeneous population, OPCs are reported to have different developmental origins and display regional and temporal diversity in their transcriptome, response to growth factors, and physiological properties. Similarly, evidence is accumulating that myelinating oligodendrocytes display transcriptional heterogeneity. Analyzing this reported heterogeneity suggests that OPCs, and perhaps also myelinating oligodendrocytes, may exist in different functional cell states. Here, we review the evidence indicating that OPCs and oligodendrocytes are diverse, and we discuss the implications of functional OPC states for myelination in the adult brain and for myelin repair.

scholarly journals Mechanisms of Glutamate Transport

2013 ◽  
Vol 93 (4) ◽  
pp. 1621-1657 ◽  
Author(s):  
Robert J. Vandenberg ◽  
Renae M. Ryan
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glutamate Transporter ◽  
Glutamate Transporters ◽  
Structural Basis ◽  
Broad Perspective ◽  
Excitatory Neurotransmitter ◽  
Brain Functions ◽  
Transporter Family ◽  
The Central Nervous System

l-Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and plays important roles in a wide variety of brain functions, but it is also a key player in the pathogenesis of many neurological disorders. The control of glutamate concentrations is critical to the normal functioning of the central nervous system, and in this review we discuss how glutamate transporters regulate glutamate concentrations to maintain dynamic signaling mechanisms between neurons. In 2004, the crystal structure of a prokaryotic homolog of the mammalian glutamate transporter family of proteins was crystallized and its structure determined. This has paved the way for a better understanding of the structural basis for glutamate transporter function. In this review we provide a broad perspective of this field of research, but focus primarily on the more recent studies with a particular emphasis on how our understanding of the structure of glutamate transporters has generated new insights.

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