Lysophosphatidic acid shifts metabolic and transcriptional landscapes to induce a distinct cellular state in human pluripotent stem cells

被引:18
作者
Xu, Faxiang [1 ]
Deng, Chunhao [1 ]
Ren, Zhili [1 ]
Sun, Liangyu [2 ]
Meng, Ya [1 ,3 ]
Liu, Weiwei [1 ,2 ]
Wan, Jianbo [4 ]
Chen, Guokai [1 ,5 ]
机构
[1] Univ Macau, Fac Hlth Sci, Ctr Reprod Dev & Aging, Macau, Peoples R China
[2] Univ Macau, Fac Hlth Sci, Bioimaging & Stem Cell Core Facil, Macau, Peoples R China
[3] Jinan Univ, Zhuhai Peoples Hosp, Ctr Intervent Radiol, Zhuhai Precis Med Ctr, Zhuhai 519000, Guangdong, Peoples R China
[4] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China
[5] Univ Macau, MoE Frontiers Sci Ctr Precis Oncol, Macau, Peoples R China
关键词
SELF-RENEWAL; CULTURE; DIFFERENTIATION; SUPPRESSION; EXPRESSION; MAINTAINS; GENES;
D O I
10.1016/j.celrep.2021.110063
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Pluripotent stem cells (PSCs) can be maintained in a continuum of cellular states with distinct features. Exogenous lipid supplements can relieve the dependence on de novo lipogenesis and shift global metabolism. However, it is largely unexplored how specific lipid components regulate metabolism and subsequently the pluripotency state. In this study, we report that the metabolic landscape of human PSCs (hPSCs) is shifted by signaling lipid lysophosphatidic acid (LPA), which naturally exists. LPA leads to a distinctive transcriptome profile that is not associated with de novo lipogenesis. Although exogenous lipids such as cholesterol, common free fatty acids, and LPA can affect cellular metabolism, they are not necessary for maintaining primed pluripotency. Instead, LPA induces distinct and reversible phenotypes in cell cycle, morphology, and mitochondria. This study reveals a distinct primed state that could be used to alter cell physiology in hPSCs
引用
收藏
页数:21
相关论文
共 43 条
[1]  
Abedpour N, 2018, VET RES FORUM, V9, P59
[2]   Evaluation of a rapid method for the quantitative analysis of fatty acids in various matrices [J].
Araujo, Pedro ;
Nguyen, Thu-Thao ;
Froyland, Livar ;
Wang, Jingdong ;
Kang, Jing X. .
JOURNAL OF CHROMATOGRAPHY A, 2008, 1212 (1-2) :106-113
[3]   Hooked on fat: the role of lipid synthesis in cancer metabolism and tumour development [J].
Baenke, Franziska ;
Peck, Barrie ;
Miess, Heike ;
Schulze, Almut .
DISEASE MODELS & MECHANISMS, 2013, 6 (06) :1353-1363
[4]   Passaging and colony expansion of human pluripotent stem cells by enzyme-free dissociation in chemically defined culture conditions [J].
Beers, Jeanette ;
Gulbranson, Daniel R. ;
George, Nicole ;
Siniscalchi, Lauren I. ;
Jones, Jeffrey ;
Thomson, James A. ;
Chen, Guokai .
NATURE PROTOCOLS, 2012, 7 (11) :2029-2040
[5]  
Binder BYK, 2015, TISSUE ENG PART B-RE, V21, P531, DOI [10.1089/ten.TEB.2015.0107, 10.1089/ten.teb.2015.0107]
[6]   Endogenous Wnt signalling in human embryonic stem cells generates an equilibrium of distinct lineage-specified progenitors [J].
Blauwkamp, Timothy A. ;
Nigam, Shelly ;
Ardehali, Reza ;
Weissman, Irving L. ;
Nusse, Roel .
NATURE COMMUNICATIONS, 2012, 3
[7]   Intracellular α-ketoglutarate maintains the pluripotency of embryonic stem cells [J].
Carey, Bryce W. ;
Finley, Lydia W. S. ;
Cross, Justin R. ;
Allis, C. David ;
Thompson, Craig B. .
NATURE, 2015, 518 (7539) :413-416
[8]  
Chen GK, 2011, NAT METHODS, V8, P424, DOI [10.1038/nmeth.1593, 10.1038/NMETH.1593]
[9]   Actin-Myosin Contractility Is Responsible for the Reduced Viability of Dissociated Human Embryonic Stem Cells [J].
Chen, Guokai ;
Hou, Zhonggang ;
Gulbranson, Daniel R. ;
Thomson, James A. .
CELL STEM CELL, 2010, 7 (02) :240-248
[10]   Lipid Mediated Regulation of Adult Stem Cell Behavior [J].
Clemot, Marie ;
Demarco, Rafael ;
Jones, D. Leanne .
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 2020, 8