Epigenetic regulation of astrocyte differentiation in the developing murine brain
Abstract
Astrocytes have numerous important roles in the developing and mature nervous system, including synapse formation, cell fate decisions and delivery of energy. Despite their relative abundance and importance in the nervous system, the mechanism of astrocyte differentiation is poorly understood. We identified stages at which the central nervous system progenitors, known as radial glial cells, generate astrocytes in the developing murine brain. We hypothesized that genes necessary for the differentiation of astrocytes could be identified in a genome-wide comparison of active genes in murine radial glial progenitors isolated at postnatal day 0 (P0) and in differentiating astrocytes isolated at P8 (postnatal day 8). Radial glial and differentiating astrocytes were isolated using magnetic bead separation of cells expressing the glutamate-aspartate transporter (GLAST). Following isolation, chromatin was immune precipitated using an antibody that binds to the acetylated lysine 9 of histone 3, an epigenetic mark that is characteristic of transcriptionally active genes within the genome. Preliminary data from the sequencing of this chromatin has shown 7763 differentially acetylated gene regions. Further analysis has identified 118 and 70 genes show greater than 1.5 fold enrichment in the cell populations at P0 and P8 respectively. The identification of the genes that show differential protein expression will reveal factors that may exclusively specify astrocytic fate. Further studies will be needed to functionally assay these genes, and identify the mechanism by which they influence astrocyte development.
Degree
M.S.
Advisors
Belecky-Adams, Purdue University.
Subject Area
Biology|Neurosciences|Cellular biology
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