Fig. 6

PG inhibits ferroptosis and promotes organ expansion.a UMAP analysis classified the intestines of hsd17b12a?/? and WT. b Proportional statistics of the six intestinal cell types in hsd17b12a?/? and WT. c Violin plots showing hsd17b12a expression profiles in six intestinal cell types. d Identification of enriched pathways for highly expressed genes in intestinal epithelial cells (p-value < 0.05). e Heatmap depicting changes in lipid components in WT and hsd17b12a?/? larvae at 4 dpf (n = 3). f Differential analysis of free LC-PUFAs (long-chain polyunsaturated fatty acids) in hsd17b12a?/? larvae compared to WT at 4 dpf. g Differential analysis of TAGs (triglycerides) containing C18:2 or C18:3 in hsd17b12a?/? larvae compared to WT at 4 dpf. h, i Differential analysis of PA (phosphatidic acid) and PG (phosphatidylglycerol) in hsd17b12a?/? larvae compared to WT at 4 dpf. j, k RT-PCR analysis of acsl4b gene expression at 5 dpf after DHA (docosahexaenoic acid), PA, and PG immersion treatments. l RT-PCR analysis of fabp2, fabp10a, and trypsin expression in WT, hsd17b12a?/?, and DHA-immersed hsd17b12a?/? at 5 dpf. m, n Images and quantification of the exocrine pancreas areas in WT, hsd17b12a?/?, and DHA-immersed hsd17b12a?/? at 5 dpf (n = 3). Scale bar, 200 ?m. o Overexpression of pgs1 rescued exocrine pancreatic expansion defects and facilitated yolk utilization in hsd17b12a?/? (n > 3). Scale bar, 250 ?m. p, q Quantification of exocrine pancreas area and yolk area at 4 dpf. Yolk area highlighted with a white dotted line. r RT-PCR analysis of acsl4b gene expression at 4 dpf following pgs1 overexpression. s Model of the DHA-PA-PG axis in the primitive intestine regulating digestive organ expansion. In hsd17b12a?/?, the LC-PUFA synthesis is blocked, leading to TAG accumulation in the yolk, decreased LC-PUFA and LC-PUFA-containing phospholipids, further resulting in ferroptosis and defective digestive organ expansion. The red arrows indicate increased content, while the blue arrows indicate decreased content. Data in f?l, n, p, q, r are represented as mean ± S.D., using a two-tailed Student?s t test; each point represents an independent biological sample (n ? 3). Source data are provided as a Source Data file.