Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord

ABSTRACTThe coordinated spatial and temporal regulation of gene expression in the vertebrate neural tube determines the identity of neural progenitors and the function and physiology of the neurons they generate. Progress has been made deciphering the gene regulatory programmes responsible for this process, however, the complexity of the tissue has hampered the systematic analysis of the network and the underlying mechanisms. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions of the developing mouse neural tube between embryonic days (e)9.5-e13.5. We confirmed the data accurately recapitulates neural tube development, allowing us to identify new markers for specific progenitor and neuronal populations. In addition, the analysis highlighted a previously underappreciated temporal component to the mechanisms generating neuronal diversity and revealed common features in the sequence of transcriptional events that lead to the differentiation of specific neuronal subtypes. Together the data provide a compendium of gene expression for classifying spinal cord cell types that will support future studies of neural tube development, function, and disease.

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Single-cell transcriptomic analysis of the adult mouse spinal cord reveals molecular diversity of autonomic and skeletal motor neurons

Nature Neuroscience ◽

10.1038/s41593-020-00795-0 ◽

2021 ◽

Vol 24 (4) ◽

pp. 572-583 ◽

Cited By ~ 1

Author(s):

Jacob A. Blum ◽

Sandy Klemm ◽

Jennifer L. Shadrach ◽

Kevin A. Guttenplan ◽

Lisa Nakayama ◽

...

Keyword(s):

Spinal Cord ◽

Single Cell ◽

Motor Neurons ◽

Molecular Diversity ◽

Adult Mouse ◽

Transcriptomic Analysis ◽

Mouse Spinal Cord

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Single cell transcriptome profiling of the human developing spinal cord reveals a conserved genetic programme with human specific features

10.1101/2021.04.12.439474 ◽

2021 ◽

Author(s):

Teresa Rayon ◽

Rory J. Maizels ◽

Christopher Barrington ◽

James Briscoe

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Single Cell ◽

Motor Neurons ◽

Neural Tube ◽

Transcriptome Profiling ◽

Cell Types ◽

Human Embryos ◽

Neuronal Populations ◽

Cell Transcriptome

AbstractThe spinal cord receives input from peripheral sensory neurons and controls motor output by regulating muscle innervating motor neurons. These functions are carried out by neural circuits comprising molecularly and physiologically distinct neuronal subtypes that are generated in a characteristic spatial-temporal arrangement from progenitors in the embryonic neural tube. The systematic mapping of gene expression in mouse embryos has provided insight into the diversity and complexity of cells in the neural tube. For human embryos, however, less information has been available. To address this, we used single cell mRNA sequencing to profile cervical and thoracic regions in four human embryos of Carnegie Stages (CS) CS12, CS14, CS17 and CS19 from Gestational Weeks (W) 4-7. In total we recovered the transcriptomes of 71,219 cells. Analysis of progenitor and neuronal populations from the neural tube, as well as cells of the peripheral nervous system, in dorsal root ganglia adjacent to the neural tube, identified dozens of distinct cell types and facilitated the reconstruction of the differentiation pathways of specific neuronal subtypes. Comparison with existing mouse datasets revealed the overall similarity of mouse and human neural tube development while highlighting specific features that differed between species. These data provide a catalogue of gene expression and cell type identity in the developing neural tube that will support future studies of sensory and motor control systems and can be explored at https://shiny.crick.ac.uk/scviewer/neuraltube/.

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Histone H1 improves regeneration after mouse spinal cord injury and changes shape and gene expression of cultured astrocytes

Restorative Neurology and Neuroscience ◽

10.3233/rnn-190903 ◽

2019 ◽

Vol 37 (4) ◽

pp. 291-313 ◽

Cited By ~ 4

Author(s):

Ralf Kleene ◽

Gabriele Loers ◽

Igor Jakovcevski ◽

Bibhudatta Mishra ◽

Melitta Schachner

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Histone H1 ◽

Mouse Spinal Cord ◽

Cultured Astrocytes ◽

Cord Injury

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Analysis of Gene Expression in Mouse Spinal Cord-derived Neural Precursor Cells During Neuronal Differentiation

Genomics & Informatics ◽

10.5808/gi.2009.7.2.085 ◽

2009 ◽

Vol 7 (2) ◽

pp. 85-96

Author(s):

Joon-Ik Ahn ◽

So-Young Kim ◽

Moon-Jeong Ko ◽

Hye-Joo Chung ◽

Ho-Sang Jeong

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Neuronal Differentiation ◽

Precursor Cells ◽

Neural Precursor Cells ◽

Neural Precursor ◽

Mouse Spinal Cord

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A harmonized atlas of mouse spinal cord cell types and their spatial organization

Nature Communications ◽

10.1038/s41467-021-25125-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Daniel E. Russ ◽

Ryan B. Patterson Cross ◽

Li Li ◽

Stephanie C. Koch ◽

Kaya J. E. Matson ◽

...

Keyword(s):

Spinal Cord ◽

Single Cell ◽

Spatial Organization ◽

Neuronal Cell ◽

Cell Types ◽

Molecular Organization ◽

Cell Type ◽

Sequencing Data ◽

Mouse Spinal Cord ◽

Common Reference

AbstractSingle-cell RNA sequencing data can unveil the molecular diversity of cell types. Cell type atlases of the mouse spinal cord have been published in recent years but have not been integrated together. Here, we generate an atlas of spinal cell types based on single-cell transcriptomic data, unifying the available datasets into a common reference framework. We report a hierarchical structure of postnatal cell type relationships, with location providing the highest level of organization, then neurotransmitter status, family, and finally, dozens of refined populations. We validate a combinatorial marker code for each neuronal cell type and map their spatial distributions in the adult spinal cord. We also show complex lineage relationships among postnatal cell types. Additionally, we develop an open-source cell type classifier, SeqSeek, to facilitate the standardization of cell type identification. This work provides an integrated view of spinal cell types, their gene expression signatures, and their molecular organization.

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Single-cell analysis of the cellular heterogeneity and interactions in the injured mouse spinal cord

Journal of Experimental Medicine ◽

10.1084/jem.20210040 ◽

2021 ◽

Vol 218 (8) ◽

Author(s):

Lindsay M. Milich ◽

James S. Choi ◽

Christine Ryan ◽

Susana R. Cerqueira ◽

Sofia Benavides ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Single Cell ◽

Single Cell Analysis ◽

Healing Process ◽

Cellular Heterogeneity ◽

Wound Healing Process ◽

Cellular Interactions ◽

Mouse Spinal Cord ◽

Cord Injury

The wound healing process that occurs after spinal cord injury is critical for maintaining tissue homeostasis and limiting tissue damage, but eventually results in a scar-like environment that is not conducive to regeneration and repair. A better understanding of this dichotomy is critical to developing effective therapeutics that target the appropriate pathobiology, but a major challenge has been the large cellular heterogeneity that results in immensely complex cellular interactions. In this study, we used single-cell RNA sequencing to assess virtually all cell types that comprise the mouse spinal cord injury site. In addition to discovering novel subpopulations, we used expression values of receptor–ligand pairs to identify signaling pathways that are predicted to regulate specific cellular interactions during angiogenesis, gliosis, and fibrosis. Our dataset is a valuable resource that provides novel mechanistic insight into the pathobiology of not only spinal cord injury but also other traumatic disorders of the CNS.

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