人类面部多样性背后的细胞类型与调控元件图谱
Atlas of cell types and regulatory elements underlying human facial diversity
人类面部形态千差万别，颅面畸形也是最常见的出生缺陷之一，但基因如何影响面部发育一直不清楚。研究者建立了胚胎第6至11周的多模态面部图谱，整合单细胞转录组、染色质可及性和空间转录组，刻画了56种细胞状态。发现面部特征相关的基因表达在早期间充质祖细胞中关联最强，随后逐渐局限到特定区域；与病理基因相关的增强子可能是现代人类面部变异的来源。研究还通过小鼠实验发现外周神经参与调控上颌骨形状。该图谱为研究颅面发育和畸形提供了重要资源。
为什么推荐给您：重要新数据资源与发育机制图谱，有转化前景，但非治疗或技术首次人体。
不需要生物学背景，多打比方
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摘要Abstract
Human genetic diversity generates an astonishing variety of facial shapes, and craniofacial anomalies rank among the most common birth defects. Identifying the cellular mechanisms that mediate the genome's influence on facial variation remains a challenge. Here we created a multimodal facial atlas across embryonic weeks 6-11, providing single-cell transcriptomics, chromatin accessibility and spatial transcriptomics, all at single-cell resolution. We characterized 56 cell states, mapping mesenchymal subtypes and their gene-enhancer cis-regulatory landscapes in space and time. Gene expression associations with facial traits were strongest in early mesenchymal progenitor cells, gradually becoming more region restricted. Autocorrelation analysis revealed patterning genes that define spatial neighborhoods of mesenchyme, potentially explaining trait specificity of their nearby variants. Enhancers of key pathology-related genes were found to be likely vehicles for generating facial variation in modern human populations. One such enhancer, linked to PAX1 expression, appears to be important for normal skeletal development in mice. Finally, facial effects inferred from the genome-wide association study, cell signaling interaction analysis and validation in mice revealed that peripheral nerves fine-tune maxilla shape during embryonic development. Together, these data offer new insights into the mechanisms underlying human phenotypic individuality and yield a multimodal atlas useful for studying craniofacial development and abnormalities.