Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, 91125, USA.
Nat Commun. 2017 Nov 28;8(1):1830. doi: 10.1038/s41467-017-01561-w.
The neural crest is an embryonic population of multipotent stem cells that form numerous defining features of vertebrates. Due to lack of reliable techniques to perform transcriptional profiling in intact tissues, it remains controversial whether the neural crest is a heterogeneous or homogeneous population. By coupling multiplex single molecule fluorescence in situ hybridization with machine learning algorithm based cell segmentation, we examine expression of 35 genes at single cell resolution in vivo. Unbiased hierarchical clustering reveals five spatially distinct subpopulations within the chick dorsal neural tube. Here we identify a neural crest stem cell niche that centers around the dorsal midline with high expression of neural crest genes, pluripotency factors, and lineage markers. Interestingly, neural and neural crest stem cells express distinct pluripotency signatures. This Spatial Genomic Analysis toolkit provides a straightforward approach to study quantitative multiplex gene expression in numerous biological systems, while offering insights into gene regulatory networks via synexpression analysis.
神经嵴是一种多能干细胞胚胎群体，形成了众多脊椎动物的特征。由于缺乏在完整组织中进行转录谱分析的可靠技术，神经嵴是异质还是同质群体仍然存在争议。通过将多重单分子荧光原位杂交与基于机器学习算法的细胞分割相结合，我们在体内以单细胞分辨率检查了 35 个基因的表达。无偏层次聚类揭示了小鸡背侧神经管内的五个空间上不同的亚群。在这里，我们确定了一个神经嵴干细胞生态位，它以背中线为中心，具有高表达的神经嵴基因、多能性因子和谱系标记物。有趣的是，神经和神经嵴干细胞表达不同的多能性特征。这种空间基因组分析工具包为研究众多生物系统中的定量多重基因表达提供了一种简单的方法，同时通过共表达分析为基因调控网络提供了深入的见解。
