Project description:Here we performed a ChIP-seq experiment for Tlx3 trancription factor on a sample of mouse embryonic dorsal spinal cord. The result is the generation of the genome-wide maps for Tlx3 binding to chromatin in dILB neurones of the developing dorsal horn.
Project description:The spinal cord possesses precise neural circuitry to transmit messages between the brain and body. Detailed transcriptomic profiling of the developing human spinal cord has not been reported. Here, we performed single cell RNA sequencing of developing human spinal cord cells and compared these data with similar mouse spinal cord RNA sequencing datasets. The differentiation tendency of proliferative neural progenitor cells changed from neuronal to glial cells at gestational week (GW) 8 and we identified a diverse set of excitatory, inhibitory and motor neuron cell types. Human ventral neuronal differentiation occurred earlier than GW7, while DI4/5 interneurons are born between GW7–11. We identified glial cell molecular diversity and revealed that ependymal cell specification occurs before birth. We also demonstrate differences between human and mouse spinal cord, including unique cell subtypes, gene expression, neurotransmitter receptors, and glial differentiation timing. Our results offer insight into human spinal cord development.
Project description:The human spinal cord contains diverse cell types, governed by a series of spatiotemporal events for tissue assembly and functions. However, the regulation of cell fate specification in the human developing spinal cord remains largely unknown. By performing single-cell and spatial multi-omics methods, we integrated the datasets and created a comprehensive human developmental atlas of the first trimester spinal cord. Unexpectedly, we discovered unique events in human spinal cord development, including early loss of active neural stem cells, simultaneous occurrence of neurogenesis and gliogenesis, and distinct spatiotemporal genetic regulations of fate choices. We also identified distinct regulations of cancer stem cells in ependymomas from our atlas. Thus, we demonstrate spatiotemporal genetic regulation of human spinal cord development and its potential to understand novel disease mechanisms.
Project description:The human spinal cord contains diverse cell types, governed by a series of spatiotemporal events for tissue assembly and functions. However, the regulation of cell fate specification in the human developing spinal cord remains largely unknown. By performing single-cell and spatial multi-omics methods, we integrated the datasets and created a comprehensive human developmental atlas of the first trimester spinal cord. Unexpectedly, we discovered unique events in human spinal cord development, including early loss of active neural stem cells, simultaneous occurrence of neurogenesis and gliogenesis, and distinct spatiotemporal genetic regulations of fate choices. We also identified distinct regulations of cancer stem cells in ependymomas from our atlas. Thus, we demonstrate spatiotemporal genetic regulation of human spinal cord development and its potential to understand novel disease mechanisms.
Project description:Despite the recognized importance of the spinal cord in sensory processing, motor behaviors, and neural diseases, the underlying organization of neuronal clusters and their spatial location remain elusive. Recently, several studies have attempted to define the neuronal types and functional heterogeneity in the spinal cord using single-cell or single-nucleus RNA sequencing in animal models or developing humans. However, molecular evidence of cellular heterogeneity in the adult human spinal cord is limited. Here, we classified spinal cord neurons into 21 subclusters and determined their distribution from nine human donors using single-nucleus RNA sequencing and spatial transcriptomics. Moreover, we compared the human findings with previously published single-nucleus data of the mouse adult spinal cord, which revealed an overall similarity in the neuronal composition of the spinal cord between the two species while simultaneously highlighting some degree of heterogeneity. Additionally, we examined the sex differences in the spinal neuronal subclusters. Several genes, such as SCN10A and HCN1, showed sex differences in motor neurons. Finally, we classified human DRG neurons using spatial transcriptomics and explored the putative interactions between DRG and spinal cord neuronal subclusters. In summary, these results illustrate the complexity and diversity of spinal neurons in humans and provide an important resource for future research to explore the molecular mechanisms underlying spinal cord physiology and diseases.