{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:18:57Z","timestamp":1792804737770,"version":"4.5.0"},"reference-count":64,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Institute of Health Carlos III","award":["AESI PI20CIII\/00015"],"award-info":[{"award-number":["AESI PI20CIII\/00015"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Institute of Health Carlos III","award":["AESI PT20CIII\/00009"],"award-info":[{"award-number":["AESI PT20CIII\/00009"]}],"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Acid sphingomyelinase deficiency (ASMD) or Niemann\u2013Pick 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.<\/jats:p>","DOI":"10.3390\/ijms241612645","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T10:11:22Z","timestamp":1691662282000},"page":"12645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis"],"prefix":"10.3390","volume":"24","author":[{"given":"Gema","family":"Gomez-Mariano","sequence":"first","affiliation":[{"name":"Molecular Genetics and Genetic Diagnostic Units, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0024-6727","authenticated-orcid":false,"given":"Sara","family":"Perez-Luz","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genetic Diagnostic Units, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4831-0353","authenticated-orcid":false,"given":"Sheila","family":"Ramos-Del Saz","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genetic Diagnostic Units, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Matamala","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genetic Diagnostic Units, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4135-860X","authenticated-orcid":false,"given":"Esther","family":"Hernandez-SanMiguel","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genetic Diagnostic Units, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3034-5723","authenticated-orcid":false,"given":"Marta","family":"Fernandez-Prieto","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genetic Diagnostic Units, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gil-Martin","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genetic Diagnostic Units, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain"},{"name":"CIBER de Enfermedades Raras, CIBERER U758, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0553-5835","authenticated-orcid":false,"given":"Iago","family":"Justo","sequence":"additional","affiliation":[{"name":"General and Digestive Surgery Department, Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Marcacuzco","sequence":"additional","affiliation":[{"name":"General and Digestive Surgery Department, Hospital 12 de Octubre, 28041 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6834-350X","authenticated-orcid":false,"given":"Beatriz","family":"Martinez-Delgado","sequence":"additional","affiliation":[{"name":"Molecular Genetics and Genetic Diagnostic Units, Institute of Rare Diseases Research (IIER), Spanish National Institute of Health Carlos III (ISCIII), 28220 Madrid, Spain"},{"name":"CIBER de Enfermedades Raras, CIBERER U758, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.beem.2014.10.002","article-title":"Types A and B Niemann-Pick disease","volume":"29","author":"Schuchman","year":"2015","journal-title":"Best Pract. 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