Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glial cell states bias the regeneration of neuron types across the newt life cycle

ABSTRACT: Salamanders have outstanding regenerative abilities, which tend to decline in post-metamorphic life stages. Among various tissues, these amphibians can regenerate the brain from ependymoglia cells, an adult neural stem cell population. Ependymoglia cells are heterogeneous; yet, whether ependymoglia cell diversity underlies variation of regenerative capacity across brain regions and life cycle stages remains poorly studied. Here we present a cell type comparison of regeneration in the pallium (dorsal telencephalon) of pre- and post-metamorphic newts. We found that ependymoglia cells exist in a continuum of cell states ranging from active proliferation to quiescence across life cycle stages, with a deep quiescence state featuring expression of mammalian astrocyte genes. Ependymoglia cell state changes are associated with a slower onset of proliferation and neurogenesis in post-metamorphic animals. Comparisons with developmental and adult neurogenesis reveal that pallial ependymoglia cells retain regional restrictions but can override temporal fate restrictions in response to an injury, producing neurons that are normally born only in early development. We thus find that brain regeneration in newts is not a simple amplification of adult neurogenesis, but a distinct process where the initial molecular state of ependymoglia cells biases the relative proportions of regenerated neuron types. Our findings establish post-metamorphic newts as a system to study how astrocyte-like glial cells can activate a neurogenic program in response to brain injury.

ORGANISM(S): Pleurodeles waltl

PROVIDER: GSE335432 | GEO | 2026/06/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Fibroblast Dedifferentiation as a Determinant of Successful Regeneration

Project description:Limb regeneration, while observed lifelong in salamanders, is restricted to pre-metamorphic stages in Xenopus laevis frogs. After amputation, post-metamorphic frogs form a blastema that grows only an unsegmented cartilage rod. Whether this loss is due to systemic factors such as the immune system or due to an intrinsic incapability of cells to form competent stem cells has been unclear. Here, we use genetic fate mapping to establish that, as in axolotl, connective tissue (CT) cells form the post-metamorphic frog blastema. Using heterochronic transplantation into the limb bud and single-cell transcriptomic profiling, we show that axolotl CT cells fully dedifferentiate and integrate to form lineages including cartilage in the developing limb. In contrast, frog blastema CT cells do not fully re-express the limb bud progenitor program, even when transplanted into the limb bud. Correspondingly, transplanted cells contribute to extraskeletal CT but not to developing cartilage. Further, using single-cell RNA-seq analysis we find that the embryonic and the adult frog cartilage differentiation programs are molecularly distinct. This work defines intrinsic restrictions in CT dedifferentiation as a limitation in adult regeneration.

2021-05-24 | GSE165901 | GEO

Epigenetic Regulation During Flatfish Metamorphosis: Integrative Omics Analysis of DNA Methylation and Gene Expression in Turbot Brain

Project description:The regulation of gene expression plays a pivotal role in the complex metamorphic process of flatfishes, which oversees the dynamic alterations that occur during their transition from a pelagic to a benthic way of life. Flatfish metamorphosis is characterized by substantial modifications in both form and function, which are initiated by thyroid hormones. Epigenetic mechanisms play a vital role in the regulation of gene expression during this transformative process. This study examines the molecular mechanisms underlying flatfish metamorphosis by integrating multi-omics data that provide information on chromatin status, DNA methylation profile, and gene expression at three key stages (pre-metamorphosis, climax and post-metamorphosis) in the turbot (Scophthalmus maximus) brain, a complex organ that plays a critical role in the regulation of this intricate process. The analysis of DNA methylation patterns revealed major epigenetic dynamic changes during the different metamorphosis stages. Specifically, the methylation levels exhibited a typical bimodal distribution in the pre-metamorphic stage, transitioned to intermediate levels of methylation (around 50%) during the climax stage, and reverted to a bimodal distribution in the post-metamorphic stage. Notably, DMRs were identified in regions of open chromatin that colocalized with CpG islands. Moreover, our results indicate an inverse relationship between DNA methylation and transcriptional activity in regions near the transcription start sites (TSSs), where high levels of methylation correspond to low expression and low levels of methylation corresponds to high gene transcription. This study thereby elucidates the regulatory impact of methylation on gene expression during the metamorphosis process in the flatfish brain.

2026-03-07 | GSE291548 | GEO

Comparison of Protein Expression During Early Phases of Limb Regeneration Between Regeneration-permissive and Regeneration-deficient Axolotl

Project description:In this project, we studied the proteomic profiles of the early stages of blastema formation of neotenic and metamorphic axolotls after limb amputation by means of LC-MS/MS technology. We quantified a total of 714 proteins having an adjusted p < 0.01 with FC greater or equal to 2 between two conditions. Principal component analysis revealed a conspicuous clustering between neotenic and metamorphic samples at 7 days post-amputation. Different set of proteins was identified as differentially expressed at all of the time points (1, 4, and 7 days post-amputations against day0) for neotenic and metamorphic stages. Although functional enrichment analyses underline the presence of common pathways between regenerative and non-regenerative stages, cell proliferation and its regulation associated pathways, immune system related pathways and muscle tissue and ECM remodeling and degradation pathways were represented at different rate between both stages.

2019-11-25 | PXD014806 | Pride

Activation of a neural stem cell transcriptional program in parenchymal astrocytes

Project description:Neural stem cells, located in discrete niches in the adult brain, generate new neurons throughout life. These stem cells are specialized astrocytes, but astrocytes in other brain regions (parenchymal astrocytes) do not generate neurons under physiological conditions. After stroke, however, astrocytes in the mouse striatum undergo neurogenesis, triggered by decreased Notch signaling. Notch signaling can be experimentally depleted in mice by deleting the Notch-mediating transcription factor Rbpj. This dataset consists of single-cell RNA sequencing data of astrocytes isolated from the striatum (where astrocytes undergo neurogenesis in response to Rbpj deletion) or somatosensory cortex (where astrocytes don't complete neurogenesis in response to Rbpj deletion) of 4 mice. Cells were isolated from Cx30-CreER; R26-tdTomato; Rbpj(fl/fl) mice at three time points after tamoxifen-induced Rbpj deletion (2, 4, 8 weeks), and from Cx30-CreER; R26-tdTomato mice with intact Rbpj 3 days after tamoxifen. These time points span the transition from astrocyte through transit-amplifying cells to neuroblasts. The dataset contains 1) astrocytes from the striatum that initiate a neurogenic transcriptional program in response to Rbpj deletion and generate transit-amplifying cells and neuroblasts, and 2) astrocytes from the somatosensory cortex that initiate a neurogenic program in response to Rbpj deletion but fail to generate transit-amplifying cells or neuroblasts.

2020-08-01 | E-MTAB-9268 | biostudies-arrayexpress

Epigenetic maintenance of neural stem cell quiescence in the adult mouse hippocampus via Setd1a [RNA-Seq]

Project description:Quiescence, a hallmark of adult neural stem cells (NSCs), is required for maintaining the NSC pool to support life-long continuous neurogenesis in the adult dentate gyrus (DG). Whether epigenetic mechanisms can maintain NSC quiescence over long term in the adult brain is not well-understood. Here we showed that adult mice with haploinsufficiency of Setd1a, a schizophrenia risk gene encoding a histone H3K4 methyltransferase, exhibited substantially enlarged DG with increased number of dentate granule cells. Deletion of Setd1a specifically in quiescent NSCs in the adult DG promoted their activation and neurogenesis, which was countered by inhibition of histone demethylase LSD1. Mechanistically, RNA sequencing and CUT & RUN analyses of cultured quiescent adult NSCs revealed Setd1a deletion-induced transcriptional changes and Setd1a targets, among which down-regulation of Bhlhe40 promoted quiescent NSC activation in the adult DG. Together, our study revealed a Setd1a-dependent epigenetic mechanism that sustains NSC quiescence in the adult DG.

2024-03-31 | GSE250276 | GEO

Epigenetic maintenance of neural stem cell quiescence in the adult mouse hippocampus via Setd1a [Cut & Run]

2024-03-31 | GSE250275 | GEO

DEK facilitates regeneration in Stroke-Injured and Aging Brain via triggering Quiescence Exit of Neural Stem Cell

Project description:Quiescent neural stem cells (NSCs) in the adult mammalian brain can, upon activation, generate neurons and glial cells that contribute to complex sensory and cognitive functions during damage repair or aging. However, the specific and sustainable determinants of quiescent NSC activation remain unclear. Here, we present DEK as the primary activator of NSC quiescence in mice, functioning via the inhibition of downstream Notch signaling pathway. Overexpression of DEK in adult NSCs triggers quiescence exit, facilitating neurogenesis, eventually leading to either the rejuvenation of aged brains or the improved damage repair in a stroke-injured model. Meanwhile, persistent DEK overexpression from embryonic stages deprives NSCs of the ability to enter quiescence, leading to the ultimate depletion of the adult NSC reservoir, causing atrophy of hippocampus and deficits in spatial learning. Our findings establish a new narrative for quiescence exit of NSCs by DEK, potentially applicable when treating neurodegenerative diseases and brain injury.

2025-06-30 | GSE200000 | GEO

Single-cell RNA-seq reveals neural progenitor subpopulations and divergent astrocyte lineages

Project description:Astrocytes are one of the most abundant cell types in the mammalian central nervous system. Their diversity was widely investigated in the adult brain recently. However, the heterogeneity of astrocyte progenitors in their early developmental stage is still not clear. In this study, we dissected the subpopulations of neural progenitor cells at the neurogenesis and the early gliogenesis stages by single-cell RNA sequencing analysis. Interestingly, we identified two astrocyte progenitor subgroups from the cerebral cortex. The astrocyte subgroups highly express Sparc or Sparcl1, which were reported have contrary functions in astrocytes to regulate synapse formation. Further analysis for subpopulations of neural progenitors from the ventral forebrain also identified two astrocyte progenitor subgroups, showing similar gene expression patterns as in the cortex. Surprisingly, clustering analysis between the subpopulations from the dorsal and the ventral forebrains showed that the astrocyte progenitors expressing Sparc or Sparcl1 were clustered together, irrespective of their derived regions. These results showed an early divergence of astrocyte progenitors and their cross-regional conservation at the start of gliogenesis during brain development.

2021-12-31 | GSE128948 | GEO

Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development

Project description:In the developing brain, neural progenitor cells (NPCs) switch the differentiation competency via changing gene expression profiles that are governed partly by epigenetic control such as histone modification, although the precise mechanism is unknown. Here we found that ESET/Setdb1/KMT1E, a histone H3 Lys-9 (H3K9) methyltransferase, was highly expressed at early stages of brain development but down-regulated over time, and that ablation of ESET led to decreased H3K9 trimethylation and misregulation of genes, resulting in severe brain defects and early lethality. In the mutant brain, endogenous retrotransposons were derepressed, and non-neural gene expression was activated. Furthermore, early neurogenesis was most severely impaired, while astrocyte formation was enhanced. We conclude that there is an epigenetic role of ESET in temporal and tissue-specific gene regulation in the developing brain. We used microarrays to identify genes up- or down- regulated when ESET is ablated in the dorsal telencephalon. We used 3 WT and 3 cKO male E14.5 embryo for each analysis

2012-08-23 | E-GEOD-40296 | biostudies-arrayexpress