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dc.contributor.author | Gomez-Mariano, Gema Maria | |
dc.contributor.author | Perez-Luz, Sara | |
dc.contributor.author | Ramos-Del Saz, Sheila | |
dc.contributor.author | Matamala, Nerea | |
dc.contributor.author | Hernandez-Sanmiguel, Esther | |
dc.contributor.author | Fernandez-Prieto, Marta | |
dc.contributor.author | Gil-Martín, Sara | |
dc.contributor.author | Justo, Iago | |
dc.contributor.author | Marcacuzco, Alberto | |
dc.contributor.author | Martinez-Delgado, Beatriz | |
dc.date.accessioned | 2023-08-29T11:20:38Z | |
dc.date.available | 2023-08-29T11:20:38Z | |
dc.date.issued | 2023-08-10 | |
dc.identifier.citation | Int J Mol Sci. 2023 Aug 10;24(16):12645. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/16371 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | This research was funded by the Institute of Health Carlos III, grants numbers AESI PI20CIII/00015 and AESI PT20CIII/00009. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Multidisciplinary Digital Publishing Institute (MDPI) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Acid sphignoimylinase deficiency (ASMD) | es_ES |
dc.subject | Niemann-Pick type B | es_ES |
dc.subject | Organoids | es_ES |
dc.subject | Liver | es_ES |
dc.subject | Lipids | es_ES |
dc.subject | Lysosome | es_ES |
dc.subject | SMPD1 gene | es_ES |
dc.subject.mesh | Niemann-Pick Disease, Type A | es_ES |
dc.subject.mesh | Niemann-Pick Diseases | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Sphingomyelins | es_ES |
dc.subject.mesh | Liver | es_ES |
dc.subject.mesh | Gene Expression | es_ES |
dc.title | Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis | es_ES |
dc.type | research article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 37628828 | es_ES |
dc.format.volume | 24 | es_ES |
dc.format.number | 16 | es_ES |
dc.format.page | 12645 | es_ES |
dc.identifier.doi | 10.3390/ijms241612645 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1422-0067 | es_ES |
dc.relation.publisherversion | https://doi.org/10.3390/ijms241612645 | es_ES |
dc.identifier.journal | International journal of molecular sciences | es_ES |
dc.repisalud.centro | ISCIII::Instituto de Investigación de Enfermedades Raras | es_ES |
dc.repisalud.institucion | ISCIII | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | info:fis/Instituto de Salud Carlos III/Programa Estatal de Generación de Conocimiento y Fortalecimiento del Sistema Español de I+D+I/Subprograma Estatal de Generación de Conocimiento/PI20-ISCIII Modalidad Proyectos de Investigacion en Salud Intramurales. (2020)/PI20CIII/00015 | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/PT20CIII/00009 | es_ES |