Adult Microglial TGFβ1 is Required for Microglia Homeostasis Via an Autocrine Mechanism to Maintain Cognitive Function in Mice

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jun 21

PMID 38906887

Authors

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 Gonzalez

J Elliott Robinson

Lucas McClain

Krishna M Roskin

Nigel H Greig

Yu Luo

Affiliations

Soon will be listed here.

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.

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