Identification of a neural crest stem cell niche by Spatial Genomic Analysis

• Published in: Nature communications 2017-11, Vol.8 (1), p.1830-11, Article 1830
• Main Authors: Lignell, Antti, Kerosuo, Laura, Streichan, Sebastian J., Cai, Long, Bronner, Marianne E.
• Format: Article
• Language: English
• Subjects: 631/136/2139; 631/1647/2017/1947; 631/378/2571; Animals; Cell Differentiation - genetics; Cell Lineage; Cell Separation; Chick Embryo; Cluster Analysis; Clustering; Embryo cells; Fluorescence; Fluorescence in situ hybridization; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation, Developmental; Gene Regulatory Networks - genetics; Genes; Genomic analysis; Genomics; Humanities and Social Sciences; In Situ Hybridization, Fluorescence - methods; Learning algorithms; Machine learning; multidisciplinary; Multiplexing; Neural crest; Neural Crest - embryology; Neural Stem Cells; Neural tube; Neural Tube - metabolism; Pluripotency; Reproducibility of Results; Science; Science (multidisciplinary); Segmentation; Spatial analysis; Stem Cell Niche - genetics; Stem cells; Subpopulations; Tissues; Transcription; Vertebrates
• ISSN: 2041-1723; 2041-1723
• 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. Neural crest cells arise within the central nervous system, then migrate and contribute to a variety of cell types. Here, the authors use multiplex transcript analysis at single cell  resolution to define neural crest and neural subpopulations within the avian neural tube, including a neural crest stem cell niche.