Gastruloid Development Competence Discriminates Different States of Pluripotency.
Gastruloid Development Competence Discriminates Different States of Pluripotency.
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DOI：
10.1016/j.stemcr.2020.12.013
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发表时间：
2021-02-09
影响因子：
5.9
通讯作者：
Patriarca EJ
中科院分区：
文献类型：
--
作者：
Cermola F;D'Aniello C;Tatè R;De Cesare D;Martinez-Arias A;Minchiotti G;Patriarca EJ
小鼠胚胎干细胞的漂浮球状聚集体可以发育成极化/拉长的类器官，即原肠。我们建立了一种高效的测定原肠形成效率(GFE)的方法，发现GFE随着多能性从初始状态(GFE≥=95%)发展到预激状态(GFE=0)而降低。具体地说，我们发现，启动的EpiSCs不能产生适当的细胞聚集体，而早期启动的EpiLCs聚集，但最终无法发育成细长的原肠。此外，我们鉴定了一种依赖于LIF的可逆的早期启动的多能性状态--脯氨酸诱导细胞(PICs)，并表明PICs能够产生原肠样细胞(GFE∼50%)，并且也有能力分化为原始生殖细胞样细胞。因此，我们建议GFE分析作为一种有价值的功能工具来区分多能性连续体的不同状态。胃突形成效率从幼稚到启动的多能性Pro诱导的细胞能够胜任胃突发育和PGC命运胃突的发育依赖于结节共受体Cripto在本文中，Minchiotti，Patriarca及其同事证明，胃突的形成为干细胞的发育保真度提供了额外的测试。这项研究揭示了LIF在提供原肠样体发育能力方面比外源的FGF/激活素具有显性作用，并提示干细胞群体中一定程度的表型异质性对于产生功能性细胞聚集体是必不可少的。
Floating spheroidal aggregates of mouse embryonic stem cells can develop into polarized/elongated organoids, namely gastruloids. We set up a high-performing assay to measure gastruloid formation efficiency (GFE), and found that GFE decreases as pluripotency progresses from naive (GFE ≥ 95%) to primed (GFE = 0) state. Specifically, we show that primed EpiSCs fail to generate proper cell aggregates, while early-primed EpiLCs aggregate but eventually fail to develop into elongated gastruloids. Moreover, we characterized proline-induced cells (PiCs), a LIF-dependent reversible early-primed state of pluripotency, and show that PiCs are able to generate gastruloids (GFE ∼ 50%) and are also competent to differentiate into primordial germ cell-like cells. Thus, we propose the GFE assay as a valuable functional tool to discriminate different states of the pluripotency continuum. Gastruloid formation efficiency lowers from naive to primed pluripotency Proline-induced cells are competent for gastruloid development and PGC fate Gastruloid development relies on the NODAL co-receptor CRIPTO In this article Minchiotti, Patriarca, and colleagues show that gastruloid formation provides an additional test of the developmental fidelity of stem cells. This study reveals that LIF exerts a dominant effect over exogenous FGF/ACTIVIN to provide gastruloid development competence, and suggests that a certain degree of phenotypic heterogeneity in the stem cell population is essential to generate functional cell aggregates.
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影响因子：
4.6
作者：
Dunn, NR;Vincent, SD;Bikoff, EK
通讯作者：
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影响因子：
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Comes, Stefania;Gagliardi, Miriam;Laprano, Nicola;Fico, Annalisa;Cimmino, Amelia;Palamidessi, Andrea;De Cesare, Dario;De Falco, Sandro;Angelini, Claudia;Scita, Giorgio;Patriarca, Eduardo J.;Matarazzo, Maria R.;Minchiotti, Gabriella
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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