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Localized EMT reprograms glial progenitors to promote spinal cord repair

ABSTRACT: Localized EMT reprograms glial progenitors to promote spinal cord repair

PROVIDER: PRJNA692492 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13447010.fastq.gz	Fastqsanger.gz
	SRR13447011.fastq.gz	Fastqsanger.gz
	SRR13447012.fastq.gz	Fastqsanger.gz
	SRR13447013.fastq.gz	Fastqsanger.gz
	SRR13447014.fastq.gz	Fastqsanger.gz

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Localized EMT reprograms glial progenitors to promote spinal cord repair [bulk RNA-seq]

Project description:Localized EMT reprograms glial progenitors to promote spinal cord repair [bulk RNA-seq]

| PRJNA692493 | ENA

Localized EMT reprograms glial progenitors to promote spinal cord repair [single-cell RNA-seq]

Project description:Localized EMT reprograms glial progenitors to promote spinal cord repair [single-cell RNA-seq]

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Localized EMT reprograms glial progenitors to promote spinal cord repair.

Project description:Anti-regenerative scarring obstructs spinal cord repair in mammals and presents a major hurdle for regenerative medicine. In contrast, adult zebrafish possess specialized glial cells that spontaneously repair spinal cord injuries by forming a pro-regenerative bridge across the severed tissue. To identify the mechanisms that regulate differential regenerative capacity between mammals and zebrafish, we first defined the molecular identity of zebrafish bridging glia and then performed cross-species comparisons with mammalian glia. Our transcriptomics show that pro-regenerative zebrafish glia activate an epithelial-to-mesenchymal transition (EMT) gene program and that EMT gene expression is a major factor distinguishing mammalian and zebrafish glia. Functionally, we found that localized niches of glial progenitors undergo EMT after spinal cord injury in zebrafish and, using large-scale CRISPR-Cas9 mutagenesis, we identified the gene regulatory network that activates EMT and drives functional regeneration. Thus, non-regenerative mammalian glia lack an essential EMT-driving gene regulatory network that reprograms pro-regenerative zebrafish glia after injury.

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Localized EMT reprograms glial progenitors to promote spinal cord repair

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-01-31 | GSE164945 | GEO

Localized EMT reprograms glial progenitors to promote spinal cord repair [bulk RNA-seq]

Project description:mCherry/EGFP double positive cells were isolated from the spinal cords of Tg(ctgfa:mCherry; gfap:EGFP) zebrafish at 5 days post injury. Bulk spinal cord tissue at 5, 10, and 21 days post-injury were also sequenced.

2021-01-31 | GSE164943 | GEO

Localized EMT reprograms glial progenitors to promote spinal cord repair [single-cell RNA-seq]

Project description:Single nuclear RNA-sequencing was performed on spinal cord tissues from Tg(gfap:EGFP) zebrafish at 1 week post injury using the 10x Genomics platform.

2021-01-31 | GSE164944 | GEO

Single-nucleus transcriptomic profiles of glial cells in human dorsal root ganglion and spinal cord

Project description:Glial cells are present throughout the entire nervous system and paly a crucial role in regulating physiological and pathological functions, such as infections, acute injuries and chronic neurodegenerative disorders. The glial cells mainly include astrocytes, microglia, and oligodendrocytes in the central nervous system (CNS), and satellite glial cells (SGCs) in the peripheral nervous system (PNS). Although the glial subtypes and functional heterogeneity is relatively well understood in mice by recent studies using single-cell or single-nucleus RNA-sequencing, no evidence yet has elucidate the transcriptomic profiles of glia cells in PNS and CNS. Here, we used high-throughput single-nucleus RNA-sequencing to map the cellular and functional heterogeneity of SGCs in human dorsal root ganglion (DRG), and astrocytes, microglia, and oligodendrocytes in human spinal cord. In addition, we compared the human findings with previous single-nucleus transcriptomic profiles of glial cells from mouse DRG and spinal cord. This work will comprehensively profile glial cells heterogeneity and will provide a powerful resource for probing the cellular basis of human physiological and pathological conditions related to glial cells.

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Project description:Salamanders have the remarkable ability to functionally regenerate after spinal cord transection. In response to injury, GFAP+ glial cells in the axolotl spinal cord proliferate and migrate to replace the missing neural tube and create a permissive environment for axon regeneration. Molecular pathways that regulate the pro-regenerative axolotl glial cell response are poorly understood. Here we show axolotl glial cells up-regulate AP-1cFos/JunB after injury, which promotes a pro-regenerative glial cell response. Axolotl glial cells directly repress c-Jun expression via up-regulation of miR-200a. Inhibition of miR-200a during regeneration causes defects in axonal regrowth and transcriptomic analysis revealed that miR-200a inhibition leads to differential regulation of genes involved with reactive gliosis, the glial scar, ECM remodeling and axon guidance. This work identifies a novel role for miR-200a in inhibiting reactive gliosis in glial cell in axolotl during spinal cord regeneration

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Expression profiling of Aldh1l1-precursors in the developing spinal cord reveals glial lineage-specific genes and direct Sox9-Nfe2l1 interactions

Project description:Developmental regulation of gliogenesis in the mammalian CNS is incompletely understood, in part due to a limited repertoire of lineage-specific genes. We used Aldh1l1-GFP as a marker for gliogenic radial glia and later-stage precursors of developing astrocytes and performed gene expression profiling of these cells. We then used this dataset to identify candidate transcription factors that may serve as glial markers or regulators of glial fate. Our analysis generated a database of developmental stage-related markers of Aldh1l1+ cells between murine embryonic day 13.5-18.5. Using these data we identify the bZIP transcription factor Nfe2l1 and demonstrate that it promotes glial fate under direct Sox9 regulatory control. Thus, this dataset represents a resource for identifying novel regulators of glial development. 18 total samples consisting of three biological replicates each of flow sorted embryonic spinal cord Aldh1l1-GFP positive cells and whole cord, spanning the radial glial to astrocyte transition

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