Cripto is essential to capture mouse epiblast stem cell and human embryonic stem cell pluripotency

被引:46
|
作者
Fiorenzano, Alessandro [1 ]
Pascale, Emilia [1 ]
D'Aniello, Cristina [1 ]
Acampora, Dario [2 ,3 ]
Bassalert, Cecilia [4 ,5 ,6 ]
Russo, Francesco [7 ]
Andolfi, Gennaro [1 ]
Biffoni, Mauro [8 ]
Francescangeli, Federica [8 ]
Zeuner, Ann [8 ]
Angelini, Claudia [7 ]
Chazaud, Claire [4 ,5 ,6 ]
Patriarca, Eduardo J. [1 ]
Fico, Annalisa [1 ]
Minchiotti, Gabriella [1 ]
机构
[1] CNR, Inst Genet & Biophys A Buzzati Traverso, Stem Cell Fate Lab, Via Pietro Castellino 111, I-80131 Naples, Italy
[2] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80131 Naples, Italy
[3] IRCCS Neuromed, I-860077 Pozzilli, IS, Italy
[4] INSERM, UMR1103, F-63001 Clermont Ferrand, France
[5] CNRS, UMR6293, F-63001 Clermont Ferrand, France
[6] Univ Clermont Auvergne, Lab GReD, BP 10448, F-63000 Clermont Ferrand, France
[7] CNR, Inst Appl Math Mauro Picone, I-80131 Naples, Italy
[8] Ist Super Sanita, Dept Hematol Oncol & Mol Med, I-00161 Rome, Italy
来源
NATURE COMMUNICATIONS | 2016年 / 7卷
关键词
PRIMITIVE ENDODERM; RNA-SEQ; DIFFERENTIATION; HETEROGENEITY; TROPHOBLAST; PROTEIN; FATE; SPECIFICATION; RESTRICTION; INDUCTION;
D O I
10.1038/ncomms12589
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Known molecular determinants of developmental plasticity are mainly transcription factors, while the extrinsic regulation of this process has been largely unexplored. Here we identify Cripto as one of the earliest epiblast markers and a key extracellular determinant of the naive and primed pluripotent states. We demonstrate that Cripto sustains mouse embryonic stem cell (ESC) self-renewal by modulating Wnt/beta-catenin, whereas it maintains mouse epiblast stem cell (EpiSC) and human ESC pluripotency through Nodal/Smad2. Moreover, we provide unprecedented evidence that Cripto controls the metabolic reprogramming in ESCs to EpiSC transition. Remarkably, Cripto deficiency attenuates ESC lineage restriction in vitro and in vivo, and permits ESC transdifferentiation into trophectoderm lineage, suggesting that Cripto has earlier functions than previously recognized. All together, our studies provide novel insights into the current model of mammalian pluripotency and contribute to the understanding of the extrinsic regulation of the first cell lineage decision in the embryo.
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页数:16
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