| Autor: |
Bedolla, Alicia, Wegman, Elliot, Weed, Max, Stevens, Messiyah K., Ware, Kierra, Paranjpe, Aditi, Alkhimovitch, Anastasia, Ifergan, Igal, Taranov, Aleksandr, Peter, Joshua D., Gonzalez, Rosa Maria Salazar, Robinson, J. Elliott, McClain, Lucas, Roskin, Krishna M., Greig, Nigel H., Luo, Yu |
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| Zdroj: |
Nature Communications; 6/21/2024, Vol. 15 Issue 1, p1-25, 25p |
| Abstrakt: |
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. TGF-β signaling is required for microglial homeostasis, however the source of ligands in the adult brain is unknown. Here, the authors show that microglial homeostasis relies on microglia-derived TGF-β1 ligand via an autocrine mechanism, which is also important for astrocyte homeostasis. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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