Dissecting human embryonic skeletal stem cell ontogeny by single-cell transcriptomic and functional analyses

Mapping the transcriptional landscape of human embryonic skeletogenesis at single-cell resolution during limb bud and primary ossification center (POC) formation. We found significant heterogeneity of stromal cells within the limb bud mesenchyme that specified proximal-distal and anterior-posterior patterning. Embryonic skeletal stem and progenitor cells first appeared during POC formation, which were highly enriched by CADM1 expression and could differentiate into osteoblasts, chondrocytes and periosteal mesenchymal stromal cells. Overall design: We performed droplet-based scRNA-seq of 42,857 cells to firstly construct a molecular landscape of skeletogenesis in human embryos

本研究以单细胞分辨率，绘制人类胚胎在肢芽与初级骨化中心（primary ossification center, POC）形成阶段的骨骼发生转录组图谱。研究发现，肢芽间充质内的基质细胞存在显著异质性，该类细胞可介导肢体近-远轴与前-后轴的模式建成。胚胎骨骼干细胞与祖细胞最早出现于初级骨化中心形成阶段，这类细胞高表达CADM1，可分化为成骨细胞、软骨细胞及骨膜间充质基质细胞。实验设计：本研究对42857个细胞开展液滴法单细胞RNA测序（single-cell RNA sequencing, scRNA-seq），首次构建人类胚胎骨骼发生的分子图谱。