| First Author | Bedolla A | Year | 2024 |
| Journal | Nat Commun | Volume | 15 |
| Issue | 1 | Pages | 5306 |
| PubMed ID | 38906887 | Mgi Jnum | J:350241 |
| Mgi Id | MGI:7661878 | Doi | 10.1038/s41467-024-49596-0 |
| Citation | Bedolla A, et al. (2024) Adult microglial TGFbeta1 is required for microglia homeostasis via an autocrine mechanism to maintain cognitive function in mice. Nat Commun 15(1):5306 |
| abstractText | While TGF-beta signaling is essential for microglial function, the cellular source of TGF-beta1 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-beta1 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-beta1 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-beta1 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-beta1 ligand derived from microglia is required for the maintenance of brain homeostasis and normal cognitive function in the adult brain. |
