Journal: Science Advances
Article Title: Pulmonary neuroendocrine cell–derived exosomes regulate iron homeostasis and oxidative stress in lung neurons
doi: 10.1126/sciadv.ady2696
Figure Lengend Snippet: ( A ) Experimental schematic showing neuronal treatment with nicotine-exposed iPNEC-derived exosomes, with or without ferristatin-II, an iron uptake inhibitor. ( B to D ) Bar graphs depict ferritin levels, ATP content, and GSH/GSSG ratios, respectively. ( E and F ) Outline showing immunocapture of SYN + exosomes from ex vivo nicotine-treated mouse lung cultures, followed by neuronal exposure with or without ferristatin-II. ( G to I ) Data indicate ferristatin-II treatment decreases ferritin accumulation, increases ATP production, and raises GSH/GSSG ratios, reflecting reduced oxidative stress. ( J ) Neuronal cells, including those with TFR1 KD were treated with immunocaptured PNEC-derived exosomes. ( K ) Immunoblot verifies efficient TFR1 KD. ( L to N ) Bar graphs show reduced ferritin, elevated ATP, and increased GSH/GSSG ratios in TFR1-deficient neurons, confirming oxidative stress reduction. ( O ) Schematic illustrating neuronal exposure to exosomes from control iPNECs, GW4869-treated iPNECs (exosome biogenesis inhibitor), or iPNECs with TF KD. ( P and Q ) Immunoblots confirm GW4869 and TF KD effects on exosome protein content. ( R to U ) Quantification reveals reduced exosome release and mitigated ferritin, ATP, and oxidative stress markers in neurons treated with modified iPNEC exosomes. ( V ) Expression of Snca and NeuN in lungs of control and P301S tau transgenic mice, with ( W ) quantified Snca expression. ( X ) Spatial transcriptomics [STARmap PLUS ] indicate enhanced neuronal vulnerability and neurodegenerative gene signatures in P301S tau transgenic mouse brains. In (B) to (D), (G) to (I), (L) to (N), (R) to (U), and (W), data are presented as means ± SEM; n = 3 independent biological replicates. Technical replicates were averaged within each experiment. Statistics: two-tailed unpaired Student’s t test for two-group comparisons, and one-way ANOVA followed by Tukey’s multiple-comparisons test for comparisons involving more than two groups. Significance levels: * P < 0.05, ** P < 0.01.
Article Snippet: The spatial transcriptomics of control and AD mouse brain were analyzed via STARmap PLUS sequencing data (Single Cell Portal of Broad Institute, Study# SCP1375) and Zenodo (DOI: 10.5281/zenodo.7332091 ) ( ).
Techniques: Derivative Assay, Ex Vivo, Western Blot, Control, Modification, Expressing, Transgenic Assay, Spatial Transcriptomics, Two Tailed Test
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![( A ) Experimental schematic showing neuronal treatment with nicotine-exposed iPNEC-derived exosomes, with or without ferristatin-II, an iron uptake inhibitor. ( B to D ) Bar graphs depict ferritin levels, ATP content, and GSH/GSSG ratios, respectively. ( E and F ) Outline showing immunocapture of SYN + exosomes from ex vivo nicotine-treated mouse lung cultures, followed by neuronal exposure with or without ferristatin-II. ( G to I ) Data indicate ferristatin-II treatment decreases ferritin accumulation, increases ATP production, and raises GSH/GSSG ratios, reflecting reduced oxidative stress. ( J ) Neuronal cells, including those with TFR1 KD were treated with immunocaptured PNEC-derived exosomes. ( K ) Immunoblot verifies efficient TFR1 KD. ( L to N ) Bar graphs show reduced ferritin, elevated ATP, and increased GSH/GSSG ratios in TFR1-deficient neurons, confirming oxidative stress reduction. ( O ) Schematic illustrating neuronal exposure to exosomes from control iPNECs, GW4869-treated iPNECs (exosome biogenesis inhibitor), or iPNECs with TF KD. ( P and Q ) Immunoblots confirm GW4869 and TF KD effects on exosome protein content. ( R to U ) Quantification reveals reduced exosome release and mitigated ferritin, ATP, and oxidative stress markers in neurons treated with modified iPNEC exosomes. ( V ) Expression of Snca and NeuN in lungs of control and P301S tau transgenic mice, with ( W ) quantified Snca expression. ( X ) Spatial transcriptomics <t>[STARmap</t> <t>PLUS</t> ] indicate enhanced neuronal vulnerability and neurodegenerative gene signatures in P301S tau transgenic mouse brains. In (B) to (D), (G) to (I), (L) to (N), (R) to (U), and (W), data are presented as means ± SEM; n = 3 independent biological replicates. Technical replicates were averaged within each experiment. Statistics: two-tailed unpaired Student’s t test for two-group comparisons, and one-way ANOVA followed by Tukey’s multiple-comparisons test for comparisons involving more than two groups. Significance levels: * P < 0.05, ** P < 0.01.](https://pub-med-central-images-cdn.bioz.com/pub_med_central_ids_ending_with_0595/pmc13060595/pmc13060595__sciadv.ady2696-f6.jpg)