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Adult microglial TGFβ1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice

Author

Listed:
  • Alicia Bedolla

    (University of Cincinnati
    University of Cincinnati)

  • Elliot Wegman

    (University of Cincinnati)

  • Max Weed

    (University of Cincinnati)

  • Messiyah K. Stevens

    (Vanderbilt University)

  • Kierra Ware

    (University of Cincinnati)

  • Aditi Paranjpe

    (Cincinnati Children’s Hospital Medical Center)

  • Anastasia Alkhimovitch

    (University of Cincinnati
    Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine)

  • Igal Ifergan

    (University of Cincinnati
    University of Cincinnati
    Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine)

  • Aleksandr Taranov

    (University of Cincinnati
    University of Cincinnati)

  • Joshua D. Peter

    (University of Cincinnati)

  • Rosa Maria Salazar Gonzalez

    (Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • J. Elliott Robinson

    (Cincinnati Children’s Hospital Medical Center
    University of Cincinnati College of Medicine)

  • Lucas McClain

    (University of Cincinnati)

  • Krishna M. Roskin

    (Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine
    University of Cincinnati College of Medicine
    Cincinnati Children’s Hospital Medical Center)

  • Nigel H. Greig

    (National Institutes of Health)

  • Yu Luo

    (University of Cincinnati
    University of Cincinnati
    Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine)

Abstract

While TGF-β signaling is essential for microglial function, the cellular source of TGF-β1 ligand and its spatial regulation remains unclear in the adult CNS. Our data supports that microglia but not astrocytes or neurons are the primary producers of TGF-β1 ligands needed for microglial homeostasis. Microglia-Tgfb1 KO leads to the activation of microglia featuring a dyshomeostatic transcriptome that resembles disease-associated, injury-associated, and aged microglia, suggesting microglial self-produced TGF-β1 ligands are important in the adult CNS. Astrocytes in MG-Tgfb1 inducible (i)KO mice show a transcriptome profile that is closely aligned with an LPS-associated astrocyte profile. Additionally, using sparse mosaic single-cell microglia KO of TGF-β1 ligand we established an autocrine mechanism for signaling. Here we show that MG-Tgfb1 iKO mice present cognitive deficits, supporting that precise spatial regulation of TGF-β1 ligand derived from microglia is required for the maintenance of brain homeostasis and normal cognitive function in the adult brain.

Suggested Citation

  • Alicia Bedolla & Elliot Wegman & Max Weed & Messiyah K. Stevens & Kierra Ware & Aditi Paranjpe & Anastasia Alkhimovitch & Igal Ifergan & Aleksandr Taranov & Joshua D. Peter & Rosa Maria Salazar Gonzal, 2024. "Adult microglial TGFβ1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49596-0
    DOI: 10.1038/s41467-024-49596-0
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