التفاصيل البيبلوغرافية
| العنوان: |
Acid Sphingomyelinase Deficiency Type B Patient-Derived Liver Organoids Reveals Altered Lysosomal Gene Expression and Lipid Homeostasis |
| المؤلفون: |
Gema Gomez-Mariano, Sara Perez-Luz, Sheila Ramos-Del Saz, Nerea Matamala, Esther Hernandez-SanMiguel, Marta Fernandez-Prieto, Sara Gil-Martin, Iago Justo, Alberto Marcacuzco, Beatriz Martinez-Delgado |
| المصدر: |
International Journal of Molecular Sciences; Volume 24; Issue 16; Pages: 12645 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2023 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
acid sphignoimylinase deficiency (ASMD), Niemann–Pick type B, organoids, liver, lipids, lysosome, SMPD1 gene |
| جغرافية الموضوع: |
agris |
| الوصف: |
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. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
Biochemistry; https://dx.doi.org/10.3390/ijms241612645Test |
| DOI: |
10.3390/ijms241612645 |
| الإتاحة: |
https://doi.org/10.3390/ijms241612645Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: |
edsbas.31DCF854 |
| قاعدة البيانات: |
BASE |
