Assistant Professor Karolinska Institutet Solna, Stockholms Lan, Sweden
Abstract: The heterogenous human neural progenitor cells (hNPCs) are the origins of specific neurons and glial cells. Their identity in the human developing spinal cord can be defined by neural patterning (NP) - a process by which hNPCs acquire distinct identities based on their specific spatial positions due to their exposure to the gradient of different signaling pathways secreted in the dorsal and ventral area. However, the unique regulations of each domain during human spinal cord NP is not fully understood yet. Recent single-cell and spatial omics show potentials to characterize such domain-specific regulations, but standard analyses method often fail to do so, due to the challenge of distinguishing "subtypes" and "transient cell states" of stem cells. Here we used early human developing neural tubes (postconceptional week 3 to 8), performed high-resolution spatial transcriptomics (Visium HD and in situ sequencing), and introduced a new bioinformatic pipeline to capture unique domain regulations in the human developing spinal cord. We identified improved outcomes of spatially organized neural stem cells during neural patterning, and achieved lineage tracing by computational methods for human spinal cord development. Therefore, our work can 1) identify the origins of different neuronal and glial subtypes during development and their distinct regulations; 2) provide new insights into mechanisms underlying neurodevelopmental disorders like neural tube defects or spinal bifida; and 3) improve stem cell therapy by guiding hNPCs toward desired neuronal or glial cell types for regeneration.
