2026-04-28T21:35:17Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/163712024-09-28T02:15:05Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19616
Repisalud
author
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-MartÃn, Sara
author
Justo, Iago
author
Marcacuzco, Alberto
author
Martinez-Delgado, Beatriz
funder
Instituto de Salud Carlos III
2023-08-29T11:20:38Z
2023-08-29T11:20:38Z
2023-08-10
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 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.
eng
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
research article
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AcidSphingomyelinaseDeficiencyType_B_2023.pdf.txt
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