摘要：SummaryThe spine has essential roles in supporting body weight, and passaging the neural elements between the body and the brain. In this study, we used integrated single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing analyses to reveal the cellular heterogeneity, lineage, and transcriptional regulatory network of the developing human spine. We found thatEPYC +HAPLN1+ fibroblasts with stem cell characteristics could differentiate into chondrocytes by highly expressing the chondrogenic markersSOX9andMATN4. Neurons could originate from neuroendocrine cells, and MEIS2 may be an essential transcription factor that promotes spinal neural progenitor cells to selectively differentiate into neurons during early gestation. Furthermore, the interaction of NRP2_SEMA3C and CD74_APP between macrophages and neurons may be essential for spinal cord development. Our integrated map provides a blueprint for understanding human spine development in the early and midgestational stages at single-cell resolution and offers a tool for investigating related diseases.Graphical abstractDisplay OmittedHighlights•scRNA-seq and scATAC-seq analyses reveal the developmental landscape of the fetal spine•Chondrocytes may originate fromEPYC +HAPLN1+ fibroblasts with stem cell characteristics•Neurons may originate from neuroendocrine cells with regulation by MEIS2Developmental biology; Biology of human development; Omics; Transcriptomics
