scRNA-sequencing in chick suggests a probabilistic model for cell fate allocation at the neural plate border.
scRNA-sequencing in chick suggests a probabilistic model for cell fate allocation at the neural plate border.
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DOI：
10.7554/elife.82717
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发表时间：
2023-08-02
期刊：
影响因子：
7.7
通讯作者：
Streit A
中科院分区：
文献类型：
--
作者：
Thiery AP;Buzzi AL;Hamrud E;Cheshire C;Luscombe NM;Briscoe J;Streit A
脊椎动物的‘神经板边界’是位于神经板边缘的一个暂时性区域，包含所有外胚层衍生物的前体：神经板、神经脊、安慰剂和表皮。在一系列脊椎动物模型中进行的优雅的功能实验提供了对外胚层内基因调控相互作用的深入了解。然而，这些在组织水平上进行的实验为单个细胞的命运分配提出了似乎相互矛盾的模型。在这里，我们对鸡外胚层从原始条纹到神经形成阶段的单细胞RNA进行了测序，以探索细胞状态的多样性和异质性。我们描述了基因模块的动态，使我们能够对外胚层命运分离时发生的分子事件的顺序进行建模。此外，我们发现以前被归类为神经板边界‘说明符’的基因通常表现出动态的表达模式，并且富含神经、神经脊或胎座命运，这表明神经板边界应该被视为一个异质的外胚层区域，而不是一个离散的过渡转录状态。对神经、神经脊和胎盘标记的分析表明，单个NPB细胞共表达竞争的转录程序，这表明它们的最终身份尚未确定。随着细胞命运的决定，这种位于边界的未决定祖细胞(BLUP)的数量逐渐减少。考虑到我们的发现，我们提出了一个在神经板边界进行细胞命运选择的概率模型。我们的数据表明，祖先的女儿对给定的外胚层衍生物做出贡献的可能性与相互竞争的转录程序的平衡有关，而相互竞争的转录程序又受祖先的时空位置调节。
The vertebrate ‘neural plate border’ is a transient territory located at the edge of the neural plate containing precursors for all ectodermal derivatives: the neural plate, neural crest, placodes and epidermis. Elegant functional experiments in a range of vertebrate models have provided an in-depth understanding of gene regulatory interactions within the ectoderm. However, these experiments conducted at tissue level raise seemingly contradictory models for fate allocation of individual cells. Here, we carry out single cell RNA sequencing of chick ectoderm from primitive streak to neurulation stage, to explore cell state diversity and heterogeneity. We characterise the dynamics of gene modules, allowing us to model the order of molecular events which take place as ectodermal fates segregate. Furthermore, we find that genes previously classified as neural plate border ‘specifiers’ typically exhibit dynamic expression patterns and are enriched in either neural, neural crest or placodal fates, revealing that the neural plate border should be seen as a heterogeneous ectodermal territory and not a discrete transitional transcriptional state. Analysis of neural, neural crest and placodal markers reveals that individual NPB cells co-express competing transcriptional programmes suggesting that their ultimate identify is not yet fixed. This population of ‘border located undecided progenitors’ (BLUPs) gradually diminishes as cell fate decisions take place. Considering our findings, we propose a probabilistic model for cell fate choice at the neural plate border. Our data suggest that the probability of a progenitor’s daughters to contribute to a given ectodermal derivative is related to the balance of competing transcriptional programmes, which in turn are regulated by the spatiotemporal position of a progenitor.
影响因子：
2.7
作者：
Ezin, Akouavi M.;Fraser, Scott E.;Bronner-Fraser, Marianne
通讯作者：
Bronner-Fraser, Marianne
影响因子：
1.2
作者：
Paxton, Christian N.;Bleyl, Steven B.;Chapman, Susan C.;Schoenwolf, Gary C.
通讯作者：
Schoenwolf, Gary C.