Eli and Edythe Broad California Institute for Regenerative Medicine Center for Regenerative Medicine and Stem Cell Research, Department of Stem Cell Biology and Regenerative Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA, 90033, USA.
Department of Rehabilitation and Regenerative Medicine, Columbia University Irving Medical Center, Columbia University, New York, NY, 10032, USA.
Nat Commun. 2022 Jan 10;13(1):13. doi: 10.1038/s41467-021-27594-w.
The cranial neural crest generates a huge diversity of derivatives, including the bulk of connective and skeletal tissues of the vertebrate head. How neural crest cells acquire such extraordinary lineage potential remains unresolved. By integrating single-cell transcriptome and chromatin accessibility profiles of cranial neural crest-derived cells across the zebrafish lifetime, we observe progressive and region-specific establishment of enhancer accessibility for distinct fates. Neural crest-derived cells rapidly diversify into specialized progenitors, including multipotent skeletal progenitors, stromal cells with a regenerative signature, fibroblasts with a unique metabolic signature linked to skeletal integrity, and gill-specific progenitors generating cell types for respiration. By retrogradely mapping the emergence of lineage-specific chromatin accessibility, we identify a wealth of candidate lineage-priming factors, including a Gata3 regulatory circuit for respiratory cell fates. Rather than multilineage potential being established during cranial neural crest specification, our findings support progressive and region-specific chromatin remodeling underlying acquisition of diverse potential.
颅神经嵴产生了巨大的多样性衍生物，包括脊椎动物头部的大部分结缔组织和骨骼组织。神经嵴细胞如何获得如此非凡的谱系潜能仍未解决。通过整合整个斑马鱼生命周期中颅神经嵴衍生细胞的单细胞转录组和染色质可及性图谱，我们观察到不同命运的增强子可及性的渐进和区域特异性建立。神经嵴衍生细胞迅速多样化为专门的祖细胞，包括多能骨骼祖细胞、具有再生特征的基质细胞、与骨骼完整性相关的独特代谢特征的成纤维细胞，以及产生用于呼吸的细胞类型的鳃特异性祖细胞。通过逆行映射谱系特异性染色质可及性的出现，我们确定了大量候选谱系启动因子，包括用于呼吸细胞命运的 Gata3 调节回路。我们的研究结果支持获得多样化潜能的基础是渐进和区域特异性染色质重塑，而不是在颅神经嵴特化期间建立多能性。
