Diverse Routes toward Early Somites in the Mouse Embryo.
Diverse Routes toward Early Somites in the Mouse Embryo.
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DOI：
10.1016/j.devcel.2020.11.013
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发表时间：
2021-01-11
影响因子：
11.8
通讯作者：
Marioni JC
中科院分区：
文献类型：
--
作者：
Guibentif C;Griffiths JA;Imaz-Rosshandler I;Ghazanfar S;Nichols J;Wilson V;Göttgens B;Marioni JC
体节的形成是创建脊椎动物节段性身体计划的基础。在这里，我们描述了在小鼠早期胚胎中形成体节的三种转录轨迹。最前面的体节前体在E7之前通过原始条纹进入，并在E7.5之前向前迁移，而第二波更后面的体节在条纹附近发展。最后，神经中胚层祖细胞(NMP)被预留用于随后的躯干体细胞发生。T-−/−嵌合胚胎的单细胞图谱显示，在没有T的情况下，前体节发育，这表明T作为近轴中胚层产生和NMP池的建立之间的守门人，具有细胞自主功能。此外，我们确定了早期T非依赖性体节的可能调节因素，并挑战了早期NMP中T-Sox2交叉拮抗模型。我们的研究强调了早期细胞类型规范中分子灵活性的概念，与多潜能干细胞分化和疾病建模具有广泛的相关性。在E8.5 Guibentif，Griffiths等人的E8.5处，多条转录轨迹支撑着体节的出现，概述了体内通往前T非依赖性体节的分子旅程，T不负向调节Sox2来控制神经输出。重建从多能小鼠上皮细胞到胚胎第8.5天存在的前体节、后体节和神经中胚祖细胞(NMP)的三个转录旅程。T−/−↔WT嵌合体的单细胞图谱验证了走向T非依赖性前体节的分子旅程，并挑战了T和SOX2相互拮抗调节NMP分化的观点。
Somite formation is foundational to creating the vertebrate segmental body plan. Here, we describe three transcriptional trajectories toward somite formation in the early mouse embryo. Precursors of the anterior-most somites ingress through the primitive streak before E7 and migrate anteriorly by E7.5, while a second wave of more posterior somites develops in the vicinity of the streak. Finally, neuromesodermal progenitors (NMPs) are set aside for subsequent trunk somitogenesis. Single-cell profiling of T−/− chimeric embryos shows that the anterior somites develop in the absence of T and suggests a cell-autonomous function of T as a gatekeeper between paraxial mesoderm production and the building of the NMP pool. Moreover, we identify putative regulators of early T-independent somites and challenge the T-Sox2 cross-antagonism model in early NMPs. Our study highlights the concept of molecular flexibility during early cell-type specification, with broad relevance for pluripotent stem cell differentiation and disease modeling. Multiple transcriptional trajectories underlie somite emergence Outlining the in vivo molecular journey toward the anterior T-independent somites T does not negatively regulate Sox2 to control neural output at E8.5 Guibentif, Griffiths et al. reconstruct three transcriptional journeys from the pluripotent mouse epiblast to anterior somites, posterior somites, and neuromesodermal progenitors (NMPs) present at embryonic day 8.5. Single-cell profiling of T−/−↔WT chimeras validates the molecular journey toward T-independent anterior somites and challenges the notion that NMP differentiation is regulated by T and Sox2 mutual antagonism.
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影响因子：
64.8
作者：
Cao, Junyue;Spielmann, Malte;Shendure, Jay
通讯作者：
Shendure, Jay
影响因子：
10.5
作者：
Kassar-Duchossoy, L;Giacone, E;Tajbakhsh, S
通讯作者：
Tajbakhsh, S
影响因子：
7.7
作者：
Dias, Andre;Lozovska, Anastasiia;Mallo, Moises
通讯作者：
Mallo, Moises
影响因子：
2.7
作者：
Chapman, DL;Agulnik, I;Papaioannou, VE
通讯作者：
Papaioannou, VE
影响因子：
--
作者：
Chesley, P
通讯作者：
Chesley, P