Neural differentiation of mouse embryonic stem cells as a tool to assess developmental neurotoxicity in vitro

2012 ◽  
Vol 33 (5) ◽  
pp. 1135-1146 ◽  
Author(s):  
Anke Visan ◽  
Katrin Hayess ◽  
Dana Sittner ◽  
Elena E. Pohl ◽  
Christian Riebeling ◽  
...  
2018 ◽  
Vol 3 (3) ◽  
pp. 133-145 ◽  
Author(s):  
Nuoya Yin ◽  
Bowen Hu ◽  
Renjun Yang ◽  
Shaojun Liang ◽  
Shengxian Liang ◽  
...  

2021 ◽  
Author(s):  
Wei Fan ◽  
Shuang Tang ◽  
Xiaojuan Fan ◽  
Yi Fang ◽  
Xiaojiang Xu ◽  
...  

AbstractSphingolipids 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.


eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Wei Fan ◽  
Shuang Tang ◽  
Xiaojuan Fan ◽  
Yi Fang ◽  
Xiaojiang Xu ◽  
...  

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.


2016 ◽  
Vol 258 ◽  
pp. S240-S241
Author(s):  
M. Rezvanfar ◽  
A. Atashi ◽  
M. Salehnia ◽  
M. Baeeri ◽  
M. Abdollahi

Biomaterials ◽  
2010 ◽  
Vol 31 (27) ◽  
pp. 7032-7042 ◽  
Author(s):  
Michel L. Dubois-Dauphin ◽  
Nicolas Toni ◽  
Stéphanie D. Julien ◽  
Igor Charvet ◽  
Lars E. Sundstrom ◽  
...  

Circulation ◽  
2006 ◽  
Vol 113 (18) ◽  
pp. 2229-2237 ◽  
Author(s):  
Xi-Min Guo ◽  
Yun-Shan Zhao ◽  
Hai-Xia Chang ◽  
Chang-Yong Wang ◽  
Ling-Ling E ◽  
...  

Thyroid ◽  
2010 ◽  
Vol 20 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Ningyi Jiang ◽  
Yingying Hu ◽  
Xiongying Liu ◽  
Yanfeng Wu ◽  
Hong Zhang ◽  
...  

2016 ◽  
Vol 25 (8) ◽  
pp. 648-659 ◽  
Author(s):  
William D'Angelo ◽  
Dhiraj Acharya ◽  
Ruoxing Wang ◽  
Jundi Wang ◽  
Chandan Gurung ◽  
...  

2017 ◽  
Vol 105 (5) ◽  
pp. 1333-1345 ◽  
Author(s):  
Laura E. Sperling ◽  
Karina P. Reis ◽  
Laura G. Pozzobon ◽  
Carolina S. Girardi ◽  
Patricia Pranke

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