Extended Data Fig. 8: TDP-43 can be released from neurons and interact with TREM2 in vitro.
a, Representative images of human iPSC derived neurons infected with AAV9.CAG.hTDP-43.GFP virus or control virus at 21 dpi. AAV1.CAG.tdTomato virus used to visualize neurons. Scale bar, 100 µm. Inserts show neuron morphology at high magnification as indicated by the area in dotted white box. White arrowheads indicate GFP-hTDP-43 translocation in neurites. Scale bar, 20 µm. b, Immunoblots of TDP-43 contained within collected culture media of iPSCs (left) or in pulled down fractions by bead-immobilized GFP antibody (right). c, Representative images of HEK 293 T cells co-transfected with myc-tagged human TREM2 (myc-hTREM2) and GFP-hTDP-43 C terminal fragment (residues 216-414) or GFP control plasmids. Scale bar, 20 µm. d, myc-hTREM2 was co-immunoprecipitated with GFP-hTDP-43 in HEK 293 T cells using bead-immobilized GFP antibody. Experiments were independently repeated three times. e, GFP-hTDP-43 was co-immunoprecipitated with myc-hTREM2 in HEK 293 T cells using bead-immobilized myc antibody. Experiments were independently repeated three times.
