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  1. Home
  3. Identification Of A Subpopulation Of Astrocyte Progenitor Cells In The Neonatal Subventricular Zone: Evidence That Migration Is Regulated By Glutamate Signaling.
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  3. Identification Of A Subpopulation Of Astrocyte Progenitor Cells In The Neonatal Subventricular Zone: Evidence That Migration Is Regulated By Glutamate Signaling.

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Identification of a Subpopulation of Astrocyte Progenitor Cells in the Neonatal Subventricular Zone: Evidence that

Zila Martinez-Lozada1,2, Alain M Guillem3, Isabella Song3

  • 1Departments of Pediatrics and Systems Pharmacology & Translational Therapeutics, The Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, PA, 19104-4318, USA. zmartinezlozada@icloud.com.

Neurochemical Research
|January 9, 2025

View abstract on PubMed

Summary
This summary is machine-generated.
Keywords:
And glutamate transportAstrocyte precursor cellsAstrocytesDevelopmentGlutamate receptorMigration

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Glial precursor cells expressing tdTomato migrate into the mouse cortex postnatally. Glutamate signaling influences this migration, with antagonists reducing migration distance and inhibitors increasing cell numbers in the cortex.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Astrocyte Biology

Background:

  • Glutamate transporter 1 (GLT1) is crucial for astrocyte function.
  • Previous studies used enhanced green fluorescent protein (eGFP) under the GLT1 gene to label adult cortical astrocytes.
  • A subpopulation of astrocytes labeled with tdTomato (tdT) under a human GLT1 promoter was not observed in early postnatal astrocyte cultures.

Purpose of the Study:

  • To characterize the developmental origins and migration patterns of tdT+ cells.
  • To investigate the molecular identity of tdT+ cells using single-cell RNA sequencing (scRNA-seq).
  • To determine the role of glutamate signaling in glial precursor cell migration into the cortex.

Main Methods:

  • Engineered mice expressing eGFP under the GLT1 gene and tdT under the human GLT1 promoter.
  • Single-cell RNA sequencing (scRNA-seq) of tdT+ cells at postnatal day 1.
  • Organotypic slice cultures to track tdT+ cell migration.
  • Pharmacological manipulation using ionotropic glutamate receptor antagonists and a pan-glutamate transporter inhibitor (TFB-TBOA).

    • Main Results:

    • At postnatal day 1, tdT+ cells were found in the subventricular zone and striatum, not the cortex, and lacked eGFP expression.
    • By postnatal day 7, tdT+ cells began appearing in the cortex and increased with age.
    • scRNA-seq revealed molecular heterogeneity in tdT+ cells, including a subpopulation expressing astrocytic markers.
    • tdT+ cells migrated into the cortex in slice cultures and subsequently expressed GLT1, NF1A, and eGFP.
    • Glutamate receptor antagonism reduced migration distance by 50%, while TFB-TBOA increased cortical tdT+ cell numbers sixfold.

    Conclusions:

    • tdT+ cells include glial progenitors that migrate into the cortex postnatally.
    • Glutamate signaling plays a significant role in controlling glial precursor cell migration.
    • This study provides novel insights into the developmental migration of astrocytes and the influence of glutamate on this process.