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SIRT1 regulates sphingolipid metabolism and neural differentiation of mouse embryonic stem cells through c-Myc-SMPDL3B

التفاصيل البيبلوغرافية
العنوان: SIRT1 regulates sphingolipid metabolism and neural differentiation of mouse embryonic stem cells through c-Myc-SMPDL3B
المؤلفون: Wei Fan, Shuang Tang, Xiaojuan Fan, Yi Fang, Xiaojiang Xu, Leping Li, Jian Xu, Jian-Liang Li, Zefeng Wang, Xiaoling Li
المصدر: eLife, Vol 10 (2021)
بيانات النشر: eLife Sciences Publications Ltd, 2021.
سنة النشر: 2021
المجموعة: LCC:Medicine
LCC:Science
LCC:Biology (General)
مصطلحات موضوعية: SIRT1, sphingomyelin degradation, embryonic stem cells, neural development, embryogenesis, c-Myc, Medicine, Science, Biology (General), QH301-705.5
الوصف: Sphingolipids are important structural components of cell membranes and prominent signaling molecules controlling cell growth, differentiation, and apoptosis. Sphingolipids are particularly abundant in the brain, and defects in sphingolipid degradation are associated with several human neurodegenerative diseases. However, molecular mechanisms governing sphingolipid metabolism remain unclear. Here, we report that sphingolipid degradation is under transcriptional control of SIRT1, a highly conserved mammalian NAD+-dependent protein deacetylase, in mouse embryonic stem cells (mESCs). Deletion of SIRT1 results in accumulation of sphingomyelin in mESCs, primarily due to reduction of SMPDL3B, a GPI-anchored plasma membrane bound sphingomyelin phosphodiesterase. Mechanistically, SIRT1 regulates transcription of Smpdl3b through c-Myc. Functionally, SIRT1 deficiency-induced accumulation of sphingomyelin increases membrane fluidity and impairs neural differentiation in vitro and in vivo. Our findings discover a key regulatory mechanism for sphingolipid homeostasis and neural differentiation, further imply that pharmacological manipulation of SIRT1-mediated sphingomyelin degradation might be beneficial for treatment of human neurological diseases.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 2050-084X
Relation: https://elifesciences.org/articles/67452; https://doaj.org/toc/2050-084X
DOI: 10.7554/eLife.67452
URL الوصول: https://doaj.org/article/7856fa2808ca493d869a8ac7f75dc326
رقم الأكسشن: edsdoj.7856fa2808ca493d869a8ac7f75dc326
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:2050084X
DOI:10.7554/eLife.67452