Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro

被引:71
|
作者
Amadei, Gianluca [1 ]
Lau, Kasey Y. C. [1 ]
De Jonghe, Joachim [2 ]
Gantner, Carlos W. [1 ]
Sozen, Berna [3 ,4 ]
Chan, Christopher [1 ]
Zhu, Meng [1 ,5 ]
Kyprianou, Christos [1 ]
Hollfelder, Florian [2 ]
Zernicka-Goetz, Magdalena [1 ,3 ]
机构
[1] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England
[2] Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England
[3] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA
[4] Yale Univ, Yale Sch Med, Dept Genet, New Haven, CT 06520 USA
[5] Harvard Med Sch, Dept Genet, Boston, MA 02215 USA
基金
英国生物技术与生命科学研究理事会; 欧洲研究理事会; 英国惠康基金;
关键词
ANTERIOR VISCERAL ENDODERM; SELF-ORGANIZATION; PLURIPOTENT CELLS; GENE; MESODERM; DIFFERENTIATION; EXPRESSION; BRACHYURY; MIGRATION; ASYMMETRY;
D O I
10.1016/j.devcel.2020.12.004
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The development of mouse embryos can be partially recapitulated by combining embryonic stemcells (ESCs), trophoblast stem cells (TS), and extra-embryonic endoderm (XEN) stem cells to generate embryo-like structures called ETX embryos. Although ETX embryos transcriptionally capture the mouse gastrula, their ability to recapitulate complex morphogenic events such as gastrulation is limited, possibly due to the limited potential of XEN cells. To address this, we generated ESCs transiently expressing transcription factor Gata4, which drives the extra-embryonic endoderm fate, and combined them with ESCs and TS cells to generate induced ETX embryos (iETX embryos). We show that iETX embryos establish a robust anterior signaling center that migrates unilaterally to break embryo symmetry. Furthermore, iETX embryos gastrulate generating embryonic and extra-embryonic mesoderm and definitive endoderm. Our findings reveal that replacement of XEN cells with ESCs transiently expressing Gata4 endows iETX embryos with greater developmental potential, thus enabling the study of the establishment of anterior-posterior patterning and gastrulation in an in vitro system.
引用
收藏
页码:366 / +
页数:26
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