Temporal single-cell transcriptomes of zebrafish spinal cord pMN progenitors reveal distinct neuronal and glial progenitor populations

AbstractBrain and spinal cord oligodendroglia have distinct functional characteristics, and cell autonomous loss of individual genes can result in different regional phenotypes. However, sequencing studies to date have not revealed distinctions between brain and spinal cord oligodendroglia. Using single-cell analysis of oligodendroglia during myelination, we demonstrate that brain and spinal cord precursors are transcriptionally distinct, defined predominantly by cholesterol biosynthesis. We further identify mechanistic target of rapamycin (mTOR) as a major regulator promoting cholesterol biosynthesis in oligodendroglia. Oligodendroglial-specific loss of mTOR compromises cholesterol biosynthesis in both the brain and spinal cord. Importantly, mTOR loss has a greater impact on cholesterol biosynthesis in spinal cord oligodendroglia that corresponds with more pronounced developmental deficits. However, loss of mTOR in brain oligodendroglia ultimately results in oligodendrocyte death, spontaneous demyelination, and impaired axonal function, demonstrating that mTOR is required for myelin maintenance in the adult brain.

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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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Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion

Science Advances ◽

10.1126/sciadv.aay6324 ◽

2020 ◽

Vol 6 (3) ◽

pp. eaay6324 ◽

Cited By ~ 15

Author(s):

Jason R. Plemel ◽

Jo Anne Stratton ◽

Nathan J. Michaels ◽

Khalil S. Rawji ◽

Eric Zhang ◽

...

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Sciatic Nerve ◽

Single Cell ◽

Peripheral Inflammation ◽

Macrophage Response ◽

Single Cell Rna Sequencing ◽

Privileged Status ◽

The Central Nervous System

Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its “immune privileged” status.

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Exploring the glial progenitor cells in the intact adult spinal cord

Neuroscience Research ◽

10.1016/j.neures.2007.06.185 ◽

2007 ◽

Vol 58 ◽

pp. S32

Author(s):

Masaaki Kitada ◽

Yutaka Itokazu ◽

Chizuka Ide ◽

Mari Dezawa

Keyword(s):

Spinal Cord ◽

Progenitor Cells ◽

Glial Progenitor Cells ◽

Adult Spinal Cord ◽

Glial Progenitor

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High-resolution single-cell imaging for functional studies in the whole brain and spinal cord and thick tissue blocks using light-emitting diode illumination

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2007.05.010 ◽

2007 ◽

Vol 164 (2) ◽

pp. 292-298 ◽

Cited By ~ 39

Author(s):

Boris V. Safronov ◽

Vitor Pinto ◽

Victor A. Derkach

Keyword(s):

Spinal Cord ◽

High Resolution ◽

Single Cell ◽

Cell Imaging ◽

Light Emitting Diode ◽

Light Emitting ◽

Functional Studies ◽

Single Cell Imaging ◽

Brain And Spinal Cord ◽

Resolution Single

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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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Identification of KLF6/PSGs and NPY-Related USF2/CEACAM Transcriptional Regulatory Networks via Spinal Cord Bulk and Single-Cell RNA-Seq Analysis

Disease Markers ◽

10.1155/2021/2826609 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Xinbing Liu ◽

Wei Gao ◽

Wei Liu

Keyword(s):

Spinal Cord ◽

Single Cell ◽

Regulatory Networks ◽

Single Cell Analysis ◽

Transcriptional Regulatory Network ◽

Transcriptional Regulator ◽

Cell Analysis ◽

Rna Seq ◽

Transcriptional Regulatory Networks ◽

Transcriptional Regulatory

Background. To further understand the development of the spinal cord, an exploration of the patterns and transcriptional features of spinal cord development in newborn mice at the cellular transcriptome level was carried out. Methods. The mouse single-cell sequencing (scRNA-seq) dataset was downloaded from the GSE108788 dataset. Single-cell RNA-Seq (scRNA-Seq) was conducted on cervical and lumbar spinal V2a interneurons from 2 P0 neonates. Single-cell analysis using the Seurat package was completed, and marker mRNAs were identified for each cluster. Then, pseudotemporal analysis was used to analyze the transcription changes of marker mRNAs in different clusters over time. Finally, the functions of these marker mRNAs were assessed by enrichment analysis and protein-protein interaction (PPI) networks. A transcriptional regulatory network was then constructed using the TRRUST dataset. Results. A total of 949 cells were screened. Single-cell analysis was conducted based on marker mRNAs of each cluster, which revealed the heterogeneity of neonatal mouse spinal cord neuronal cells. Functional analysis of pseudotemporal trajectory-related marker mRNAs suggested that pregnancy-specific glycoproteins (PSGs) and carcinoembryonic antigen cell adhesion molecules (CEACAMs) were the core mRNAs in cluster 3. GSVA analysis then demonstrated that the different clusters had differences in pathway activity. By constructing a transcriptional regulatory network, USF2 was identified to be a transcriptional regulator of CEACAM1 and CEACAM5, while KLF6 was identified to be a transcriptional regulator of PSG3 and PSG5. This conclusion was then validated using the Genotype-Tissue Expression (GTEx) spinal cord transcriptome dataset. Conclusions. This study completed an integrated analysis of a single-cell dataset with the utilization of marker mRNAs. USF2/CEACAM1&5 and KLF6/PSG3&5 transcriptional regulatory networks were identified by spinal cord single-cell analysis.

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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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