Effects at the transcriptomic level after knockout of Eed, Ezh2, Brd8 or Nr6a1 in spinal cord neural progenitor differentiation [bulkRNAseq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE264171 | GEO | 2024/04/22
REPOSITORIES: GEO
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Project description:The vertebrate neural tube generates a large diversity of molecularly and functionally distinct neurons and glia from a small progenitor pool. While the role of spatial patterning in organising cell fate specification has been extensively studied, temporal patterning, which controls the timing of cell type generation, is equally important. Here we define a global temporal programme in the spinal cord. This governs cell fate choices by regulating chromatin accessibility in neural progenitors. Perturbation of this cis-regulatory programme affects sequential transitions in spinal cord progenitors and the identity of progeny. The temporal programme operates in parallel to spatial patterning, ensuring the timely availability of regulatory elements for spatial determinants to direct cell-type specific gene expression. These findings identify a chronotopic spatiotemporal integration strategy in which a global temporal chromatin programme determines the output of a spatial gene regulatory network resulting in the temporally and spatially ordered allocation of cell type identity.
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Project description:The vertebrate neural tube generates a large diversity of molecularly and functionally distinct neurons and glia from a small progenitor pool. While the role of spatial patterning in organising cell fate specification has been extensively studied, temporal patterning, which controls the timing of cell type generation, is equally important. Here we define a global temporal programme in the spinal cord. This governs cell fate choices by regulating chromatin accessibility in neural progenitors. Perturbation of this cis-regulatory programme affects sequential transitions in spinal cord progenitors and the identity of progeny. The temporal programme operates in parallel to spatial patterning, ensuring the timely availability of regulatory elements for spatial determinants to direct cell-type specific gene expression. These findings identify a chronotopic spatiotemporal integration strategy in which a global temporal chromatin programme determines the output of a spatial gene regulatory network resulting in the temporally and spatially ordered allocation of cell type identity.
2024-04-22 | GSE264170 | GEO
Project description:The vertebrate neural tube generates a large diversity of molecularly and functionally distinct neurons and glia from a small progenitor pool. While the role of spatial patterning in organising cell fate specification has been extensively studied, temporal patterning, which controls the timing of cell type generation, is equally important. Here we define a global temporal programme in the spinal cord. This governs cell fate choices by regulating chromatin accessibility in neural progenitors. Perturbation of this cis-regulatory programme affects sequential transitions in spinal cord progenitors and the identity of progeny. The temporal programme operates in parallel to spatial patterning, ensuring the timely availability of regulatory elements for spatial determinants to direct cell-type specific gene expression. These findings identify a chronotopic spatiotemporal integration strategy in which a global temporal chromatin programme determines the output of a spatial gene regulatory network resulting in the temporally and spatially ordered allocation of cell type identity.
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Project description:Among the vertebrates, teleost and urodele amphibians are capable of regenerating their central nervous system. We have used crush injury method on zebrafish spinal cord, which is a common mammalian mode of injury in spinal cord. To identify the molecular mechanisms of the underlying cellular events during regeneration of zebrafish spinal cord, we have employed high density oligonucleotide microarrays and profiled the temporal transcriptome dynamics during the entire phenomenon. A total of 3842 genes expressed differentially with significant fold changes during spinal cord regeneration. Cluster analysis revealed event specific dynamic expression of genes related to inflammation, cell death, cell migration, cell proliferation, neurogenesis, neural patterning and axonal regrowth. We have also validated the expression pattern of 14 genes (which include inflammatory regulators, cell cycle regulators, pattern forming genes and signaling molecules) by different methodologies. Spatio-temporal analysis of STAT3 expression suggested its possible function in controlling inflammation and cell proliferation. Genes involved in the proliferating neural progenitors and their dorso-ventral patterning (sox2 and dbx2) are differentially expressed. Injury induced cell proliferation is controlled by many cell cycle regulators and some of them also show their common expression in other regenerating systems like fin, heart and retina. We also reported unusual expression pattern of certain pathway genes like one carbon folate metabolism and N-glycan biosynthesis which have not been reported during regeneration of spinal cord. Genes like stat3, socs3, atf3, mmp9 and sox11, which are known to control peripheral nervous system (PNS) regeneration in mammals, are also upregulated in zebrafish spinal cord injury (SCI) thus creating PNS like environment after injury. Our study provides a comprehensive genetic blue print of diverse cellular response(s) during regeneration of zebrafish spinal cord that could be used to induce successful regeneration in mammals. The spinal cord has been injured by crushing dorso-ventrally for 1 sec with a number 5 Dumont forceps at the level of 15th/16th vertebrae. Later the wound were sealed by placing a suture. Both spinal cord injured and sham operated fish were allowed to regenerate and the progress of regeneration was observed after 1, 3, 7, 10 and 15 days of injury. Zebrafishes were anesthetized deeply for 5 minutes in 0.1% tricaine (MS222; Sigma, USA) and approximately 1mm length of spinal cord both rostrally and caudally from injury epicenter were dissected out from 50-60 fishes in each batch and pooled for RNA extraction.
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Project description:Among the vertebrates, teleost and urodele amphibians are capable of regenerating their central nervous system. We have used crush injury method on zebrafish spinal cord, which is a common mammalian mode of injury in spinal cord. To identify the molecular mechanisms of the underlying cellular events during regeneration of zebrafish spinal cord, we have employed high density oligonucleotide microarrays and profiled the temporal transcriptome dynamics during the entire phenomenon. A total of 3842 genes expressed differentially with significant fold changes during spinal cord regeneration. Cluster analysis revealed event specific dynamic expression of genes related to inflammation, cell death, cell migration, cell proliferation, neurogenesis, neural patterning and axonal regrowth. We have also validated the expression pattern of 14 genes (which include inflammatory regulators, cell cycle regulators, pattern forming genes and signaling molecules) by different methodologies. Spatio-temporal analysis of STAT3 expression suggested its possible function in controlling inflammation and cell proliferation. Genes involved in the proliferating neural progenitors and their dorso-ventral patterning (sox2 and dbx2) are differentially expressed. Injury induced cell proliferation is controlled by many cell cycle regulators and some of them also show their common expression in other regenerating systems like fin, heart and retina. We also reported unusual expression pattern of certain pathway genes like one carbon folate metabolism and N-glycan biosynthesis which have not been reported during regeneration of spinal cord. Genes like stat3, socs3, atf3, mmp9 and sox11, which are known to control peripheral nervous system (PNS) regeneration in mammals, are also upregulated in zebrafish spinal cord injury (SCI) thus creating PNS like environment after injury. Our study provides a comprehensive genetic blue print of diverse cellular response(s) during regeneration of zebrafish spinal cord that could be used to induce successful regeneration in mammals.
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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.
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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.
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