A transcriptome-based assessment of the astrocytic dystrophin-associated complex in the developing human brain

Matthew J. Simon, Charles Murchison, Jeffrey Iliff

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Astrocytes play a critical role in regulating the interface between the cerebral vasculature and the central nervous system. Contributing to this is the astrocytic endfoot domain, a specialized structure that ensheathes the entirety of the vasculature and mediates signaling between endothelial cells, pericytes, and neurons. The astrocytic endfoot has been implicated as a critical element of the glymphatic pathway, and changes in protein expression profiles in this cellular domain are linked to Alzheimer's disease pathology. Despite this, basic physiological properties of this structure remain poorly understood including the developmental timing of its formation, and the protein components that localize there to mediate its functions. Here we use human transcriptome data from male and female subjects across several developmental stages and brain regions to characterize the gene expression profile of the dystrophin-associated complex (DAC), a known structural component of the astrocytic endfoot that supports perivascular localization of the astroglial water channel aquaporin-4. Transcriptomic profiling is also used to define genes exhibiting parallel expression profiles to DAC elements, generating a pool of candidate genes that encode gene products that may contribute to the physiological function of the perivascular astrocytic endfoot domain. We found that several genes encoding transporter proteins are transcriptionally associated with DAC genes.

Original languageEnglish (US)
JournalJournal of Neuroscience Research
DOIs
StateAccepted/In press - 2017

Fingerprint

Dystrophin
Transcriptome
Brain
Genes
Aquaporin 4
Gene Pool
Pericytes
Aquaporins
Proteins
Astrocytes
Alzheimer Disease
Central Nervous System
Endothelial Cells
Pathology
Neurons

Keywords

  • AQP4
  • Astrocytes
  • Dystrophin-associated complex
  • Glymphatic
  • Perivascular endfoot
  • SCR_003302
  • SCR_008083
  • SCR_010943

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

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abstract = "Astrocytes play a critical role in regulating the interface between the cerebral vasculature and the central nervous system. Contributing to this is the astrocytic endfoot domain, a specialized structure that ensheathes the entirety of the vasculature and mediates signaling between endothelial cells, pericytes, and neurons. The astrocytic endfoot has been implicated as a critical element of the glymphatic pathway, and changes in protein expression profiles in this cellular domain are linked to Alzheimer's disease pathology. Despite this, basic physiological properties of this structure remain poorly understood including the developmental timing of its formation, and the protein components that localize there to mediate its functions. Here we use human transcriptome data from male and female subjects across several developmental stages and brain regions to characterize the gene expression profile of the dystrophin-associated complex (DAC), a known structural component of the astrocytic endfoot that supports perivascular localization of the astroglial water channel aquaporin-4. Transcriptomic profiling is also used to define genes exhibiting parallel expression profiles to DAC elements, generating a pool of candidate genes that encode gene products that may contribute to the physiological function of the perivascular astrocytic endfoot domain. We found that several genes encoding transporter proteins are transcriptionally associated with DAC genes.",
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