2026-04-28T21:35:17Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/163712024-09-28T02:15:05Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616

00925njm 22002777a 4500 dc Gomez-Mariano, Gema Maria author Perez-Luz, Sara author Ramos-Del Saz, Sheila author Matamala, Nerea author Hernandez-SanMiguel, Esther author Fernandez-Prieto, Marta author Gil-Martín, Sara author Justo, Iago author Marcacuzco, Alberto author Martinez-Delgado, Beatriz author 2023-08-10 Acid sphingomyelinase deficiency (ASMD) or Niemann-Pick disease type A (NPA), type B (NPB) and type A/B (NPA/B), is a rare lysosomal storage disease characterized by progressive accumulation of sphingomyelin (SM) in the liver, lungs, bone marrow and, in severe cases, neurons. A disease model was established by generating liver organoids from a NPB patient carrying the p.Arg610del variant in the SMPD1 gene. Liver organoids were characterized by transcriptomic and lipidomic analysis. We observed altered lipid homeostasis in the patient-derived organoids showing the predictable increase in sphingomyelin (SM), together with cholesterol esters (CE) and triacylglycerides (TAG), and a reduction in phosphatidylcholine (PC) and cardiolipins (CL). Analysis of lysosomal gene expression pointed to 24 downregulated genes, including SMPD1, and 26 upregulated genes that reflect the lysosomal stress typical of the disease. Altered genes revealed reduced expression of enzymes that could be involved in the accumulation in the hepatocytes of sphyngoglycolipids and glycoproteins, as well as upregulated genes coding for different glycosidases and cathepsins. Lipidic and transcriptome changes support the use of hepatic organoids as ideal models for ASMD investigation. Int J Mol Sci. 2023 Aug 10;24(16):12645. http://hdl.handle.net/20.500.12105/16371 37628828 10.3390/ijms241612645 1422-0067 International journal of molecular sciences Acid sphignoimylinase deficiency (ASMD) Niemann-Pick type B Organoids Liver Lipids Lysosome SMPD1 gene Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis