Extended Data Fig. 3: Related to Figure 3. | Nature Metabolism

Extended Data Fig. 3: Related to Figure 3.

From: Hepatic gluconeogenesis and PDK3 upregulation drive cancer cachexia in flies and mice

Extended Data Fig. 3

. (a) Total expression of gluconeogenesis pathway genes in each cell cluster. Gluconeogenesis pathway genes are retrieved from Kyoto Encyclopedia of Genes and Genomes (KEGG), include Ald1, Ald2, CG7059, CG9010, CG9961, Eno, fbp, G6P, Gapdh1, Gapdh2, Pepck1, Pepck2, Pgk, Pglym78, Pglym87, Tpi, Tps1, Pdk (00 _epithelial_cell n=12066, 01_muscle_cell n=10791, 02_indirect_flight_muscle n=21190, 03_heart_muscle n=381, 04_visceral_muscle_of_midgut n=1064, 05 _intestinal_stem_cell n=4066, 06_enterocyte n=4583, 07 _enterocyte-like n=674, 08_enteroendocrine_cell n=264, 09_cardia n=715, 10_hindgut_A n=2650, 11_hindgut_B n=1732, 12_hindgut_C n=621, 13_fat_body n=6200, 14_oenocyte n=3597, 15_hemocyte n=2468, 16 _tracheal _cell n=2344, 17_malpighian_tubule_principal_cell n=780, 18_salivary_gland n=562, 19_ventral_nervous_system n=7585, 20_cell_body _glial_cell n=1827, 21_follicle_cell n=15600, 22_follicle_cell _stage 9+* n=1994, 23 _stretch_follicle_cell n=779, 24 _stalk_follicle_cell n=1954, 25_cyst_stem_cells n=662, 26_germline_cell_A_unknown stage n=6615, 27_germline_cell_B_germline cyst n=3518, 28 _germline_cell_C_unknown stage n=3130, 29_oviduct n=723, 30_female_reproductive_system_A n=1294, 31_female_reproductive_system_B n=48, 32_neuron_A n=77, 33_neuron_B n=236). Box plots denote the medians, means, and the interquartile range. The whiskers of each box plot are the lowest and highest expression levels. UMAP visualization of expression levels of Tps1 (b) and G6p (c) across all cell clusters retrieved from snRNA-seq. (d) Representative gut tumor and phenotypes of Yki flies induced by indicated methods (esg-Gal4>UAS-Yki, esg-LexA>LexAop-Yki 2nd, and esg-LexA>LexAop-Yki 3rd). The experiment was repeated two times independently, producing similar results. Whole-body glycogen (e), TAG (f), levels of control flies, Yki flies, and Yki flies with fat body Pepck1 depletion at Day 6 (n=4). Whole-body glycogen (g), TAG (h), levels of control flies, Yki flies, and Yki flies with fat body Pdk depletion at Day 6 (n=4). (i) Whole-body trehalose levels of control flies, Yki flies, and Yki flies with fat body Pdk depletion at Day 2 and Day 4 (n=4). Raw metabolite reads and normalized proportions of 13C3 labeled oxaloacetate (j) and phosphoenolpyruvate (k) (Ctrl n=4, Yki n=4, Yki with fat body Pdk depletion n=6). Statistical significance was assessed by ordinary one-way ANOVA (e-g, i). ns indicates not significant. Error bars indicate SDs with the mean as the center.

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