Pajanoja Ceren, Hsin Jenny, Olinger Bradley, Schiffmacher Andrew, Abrams Shaun, Dapkunas Arvydas, Zainul Zarin, Doyle Andrew D, Martin Daniel, Kerosuo Laura
National Institute of Dental and Craniofacial Research, Intramural Research Program, Neural Crest Development and Disease Unit, National Institutes of Health, Bethesda, USA.
University of Helsinki, Faculty of Medicine, Helsinki, Finland.
Res Sq. 2023 Jan 25:rs.3.rs-2285117. doi: 10.21203/rs.3.rs-2285117/v1.
The ability of the pluripotent epiblast to contribute progeny to all three germ layers is thought to be lost after gastrulation. The later-forming neural crest (NC) rises from ectoderm and it remains poorly understood how its exceptionally high stem-cell potential to generate mesodermal- and endodermal-like cells is obtained. We monitored transcriptional changes from gastrulation to neurulation using single-cell-Multiplex-Spatial-Transcriptomics (scMST) complemented with RNA-sequencing. Unexpectedly, we find maintenance of undecided Nanog/Oct4-PouV/Klf4-positive pluripotent-like pan-ectodermal stem-cells spanning the entire ectoderm late in the neurulation process with ectodermal patterning completed only at the end of neurulation when pluripotency becomes restricted to NC, challenging our understanding of gastrulation. Furthermore, broad ectodermal pluripotency is found at all axial levels unrelated to the NC lineage the cells later commit to, suggesting a general role in stemness enhancement and proposing a mechanism by which the NC acquires its ability to form derivatives beyond "ectodermal-capacity" in chick and mouse embryos.
多能外胚层向所有三个胚层贡献后代的能力被认为在原肠胚形成后丧失。后来形成的神经嵴（NC）起源于外胚层，其产生中胚层样和内胚层样细胞的异常高的干细胞潜能是如何获得的，目前仍知之甚少。我们使用单细胞多重空间转录组学（scMST）并结合RNA测序监测了从原肠胚形成到神经胚形成的转录变化。出乎意料的是，我们发现在神经胚形成过程后期，未分化的Nanog/Oct4-PouV/Klf4阳性多能样全外胚层干细胞在整个外胚层中持续存在，外胚层模式仅在神经胚形成结束时完成，此时多能性仅限于神经嵴，这挑战了我们对原肠胚形成的理解。此外，在与细胞后来所进入的神经嵴谱系无关的所有轴向水平上都发现了广泛的外胚层多能性，这表明其在增强干性方面具有普遍作用，并提出了一种机制，通过该机制神经嵴在鸡和小鼠胚胎中获得形成超出“外胚层能力”的衍生物的能力。
