Integrated single-cell analyses decode the developmental landscape of the human fetal spine

The 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 sin-gle-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing analyses to reveal the cellular heterogeneity, lineage, and transcrip-tional regulatory network of the developing human spine. We found that EPYC + HAPLN1+ fibroblasts with stem cell characteristics could differentiate into chondrocytes by highly expressing the chondrogenic markers SOX9 and MATN4. 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 neu-rons may be essential for spinal cord development. Our integrated map provides a blueprint for understanding human spine development in the early and midges-tational stages at single-cell resolution and offers a tool for investigating related diseases.

Automated summary

This study used integrated single-cell RNA sequencing and single-cell transposase-accessible chromatin sequencing analyses to investigate cellular heterogeneity and transcriptional regulatory networks during human spine development. The findings revealed that fibroblasts with stem cell characteristics can differentiate into chondrocytes and neurons may originate from neuroendocrine cells. The interaction between macrophages and neurons involving NRP2_SEMA3C and CD74_APP is crucial for spinal cord development.