Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro.
Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro.
复制标题
DOI：
10.1016/j.devcel.2020.12.004
复制
发表时间：
2021-02-08
影响因子：
11.8
通讯作者：
Zernicka-Goetz M
中科院分区：
文献类型：
--
作者：
Amadei G;Lau KYC;De Jonghe J;Gantner CW;Sozen B;Chan C;Zhu M;Kyprianou C;Hollfelder F;Zernicka-Goetz M
小鼠胚胎的发育可以通过结合胚胎干细胞(ESCs)、滋养层干细胞(TS)和胚胎外内胚层(XEN)干细胞来产生被称为ETX胚胎的类似胚胎的结构来部分概括。尽管ETX胚胎在转录上捕获了小鼠的原肠胚，但它们重现复杂形态发生事件(如原肠形成)的能力有限，可能是由于Xen细胞的潜力有限。为了解决这个问题，我们产生了瞬时表达转录因子Gata4的ESCs，它驱动着胚胎外内胚层的命运，并将它们与ESCs和TS细胞结合起来，产生诱导ETX胚胎(iETX胚胎)。我们表明，iETX胚胎建立了一个强大的前信号中心，该中心单方面迁移来破坏胚胎的对称性。此外，iETX胚胎原肠形成胚胎和胚胎外的中胚层和最终的内胚层。我们的发现表明，用瞬时表达Gata4的ESCs取代Xen细胞可以赋予iETX胚胎更大的发育潜力，从而使体外系统中建立前后构型和原肠形成的研究成为可能。干细胞产生的小鼠胚胎样结构具有改进的潜能，这些结构承担着内脏前内胚层的形成和原肠形成，单细胞测序显示这些结构与小鼠胚胎Amadei等人的相似程度提高。已经产生了类似于小鼠植入后胚胎的干细胞结构，并有可能在体外形成前后轴并经历原肠形成。单细胞测序显示的基因表达模式类似于处于可比发育阶段的自然胚胎。
The development of mouse embryos can be partially recapitulated by combining embryonic stem cells (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. Stem cells generate mouse-embryo-like structures with improved potential These structures undertake anterior visceral endoderm formation and gastrulation Single-cell sequencing shows improved resemblance to mouse embryo Amadei et al. have generated stem-cell-based structures that resemble mouse post-implantation embryos and have the potential to form the anterior-posterior axis and undergo gastrulation in vitro. Single-cell sequencing shows gene-expression patterns similar to those of the natural embryo at a comparable stage of development.
登录
查看更多内容
影响因子：
7.7
作者：
Morgani SM;Metzger JJ;Nichols J;Siggia ED;Hadjantonakis AK
通讯作者：
Hadjantonakis AK
影响因子：
21.3
作者：
Boroviak T;Loos R;Bertone P;Smith A;Nichols J
通讯作者：
Nichols J
影响因子：
4.6
作者：
Mesnard, Daniel;Guzman-Ayala, Marcela;Constam, Daniel B.
通讯作者：
Constam, Daniel B.
影响因子：
64.8
作者：
Brennan, J;Lu, CC;Robertson, EJ
通讯作者：
Robertson, EJ
影响因子：
3.4
作者：
Mathew, Biena;Munoz-Descalzo, Silvia;Fischer, Sabine C.
通讯作者：
Fischer, Sabine C.