Identification of region-specific astrocyte subtypes at single cell resolution
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE114000 | GEO | 2019/12/13
REPOSITORIES: GEO
Similar Datasets
Project description:We isolated and gene expression profiled distinct astrocyte subtypes from three central nervous system regions: forebrain, hindbrain, and spinal cord, using a FACS-based protocol. Cell surface expression of Glast/Slc1a3 (G) and Acsa-2/Atp1b2 (A) was used to distinguish subpopulations of astrocytes. Furthermore, we assessed the transcriptome of cultured primary neonatal astrocytes. The local brain environment proved key in establishing different transcriptional programs in astrocyte subtypes. Functional differences between subtypes were also apparent in experimental autoimmune encephalomyelitics (EAE) mice, where these astrocyte subtypes showed distinct responses. While gene expression signatures associated with blood-brain-barrier maintenance were lost during EAE, signatures contributing to neuroinflammation were increased specifically in astrocytes in the spinal cord.
2021-01-18 | GSE136358 | GEO
Project description:Astrocytes, the most abundant cells in the central nervous system, promote synapse formation and help refine neural connectivity. Although they are allocated to spatially distinct regional domains during development, it is unknown whether region-restricted astrocytes are functionally heterogeneous. Here we show that postnatal spinal cord astrocytes express several region-specific genes, and that ventral astrocyte-encoded Semaphorin3a (Sema3a) is required for proper motor neuron and sensory neuron circuit organization. Loss of astrocyte-encoded Sema3a led to dysregulated α−motor neuron axon initial segment orientation, markedly abnormal synaptic inputs, and selective death of α−but not of adjacent γ−motor neurons. Additionally, a subset of TrkA+ sensory afferents projected to ectopic ventral positions. These findings demonstrate that stable maintenance of a positional cue by developing astrocytes influences multiple aspects of sensorimotor circuit formation. More generally, they suggest that regional astrocyte heterogeneity may help to coordinate postnatal neural circuit refinement. 12 total samples consisting of three biological replicates each of flow sorted postnatal day 7 dorsal spinal cord astrocytes, ventral spinal cord astrocytes, dorsal SC non astrocytes, and ventral SC non astrocytes
2014-05-02 | E-GEOD-55054 | biostudies-arrayexpress
Project description:Heterogeneous astrocyte populations are defined by diversity in cellular environment, progenitor identity or function. Yet, little is known about the extent of the heterogeneity and how this diversity is acquired during development. We used SILAC and quantitative proteomics to characterise primary murine telencephalic progenitor cells from FOXG1 (forkhead box G1)-cre driven Tgfbr2 (transforming growth factor beta receptor 2) knockout mice and identified differential protein expression of the astrocyte proteins GFAP (glial fibrillary acidic protein) and MFGE8 (milk fat globule-EGF factor 8). Biochemical and histological investigations revealed distinct populations of astrocytes in the dorsal and ventral telencephalon marked by GFAP or MFGE8 protein expression. The two subtypes differed in their response to TGFβ-signalling. Impaired TGFβ-signalling affected numbers of GFAP-astrocytes in the ventral telencephalon. In contrast, TGFβ reduced MFGE8 expression in astrocytes deriving from both regions. Additionally, lineage tracing revealed that both GFAP and MFGE8 astrocyte subtypes derived partly from FOXG1-expressing neural precursor cells.
2022-03-02 | PXD005072 | Pride
Project description:The glial environment determines the outcome of neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known if and when they are present in human brain pathology. Here, we examined a broad spectrum of pathologies with and without intracerebral hemorrhage and found a striking correlation between lesions involving blood-brain barrier rupture and astrocyte proliferation that was further corroborated in an assay probing for neural stem cell potential. Most importantly, proteomic analysis unraveled a crucial signaling pathway regulating this astrocyte plasticity with GALECTIN3 as a novel marker for proliferating astrocytes and the GALECTIN3-binding protein LGALS3BP as a functional hub mediating astrocyte proliferation and neurosphere formation. Taken together, this work identifies a therapeutically relevant astrocyte response and their molecular regulators in different pathologies affecting the human cerebral cortex.
2023-12-08 | PXD045579 | Pride
Project description:Astrocytes within specific brain regions contribute uniquely to regional circuits for higher-order brain function through interactions with local neurons. The regional diversification of astrocytes is dictated by their embryonic origin, yet the mechanisms governing their regional allocation remain unknown. Here we show that allocation of astrocytes to specific brain regions requires the transcription factor 4 (Tcf4) mediated fate restriction during brain development. Loss of Tcf4 in ventral telencephalic neural progenitors alters the fate of oligodendrocyte precursors to transient intermediate astrocyte precursor cells, resulting in mislocated astrocytes in the dorsal neocortex. These ectopic astrocytes originated from the ventral telencephalon engage with neurons and acquire features reminiscent of local neocortical astrocytes. Furthermore, Tcf4 functions as a suppressor of astrocyte fate during differentiation of oligodendrocyte precursors, thereby restricting the fate to oligodendrocyte lineage. Our study reveals that fate restriction governs regional astrocyte allocation, contributing to astrocyte diversification across brain regions.
2024-08-14 | GSE244709 | GEO
Project description:Normal brain aging is marked by a cognitive decline, spurred by changes in cellular metabolism and homeostatic dysregulation, as well as modifications in synapses and neuronal connectivity. Astrocytes are well positioned as an effector of these changes, although how properties of astrocytes change with age remains unclear. Here, we address this question by profiling astrocytic gene expression from multiple brain regions of adult (4 month-old) and aged (2 years-old) mice. We isolated mRNA from transgenic mice where ribosomes within astrocytes were genetically tagged (GFAP-cre x RPL22-HA, astrocyte ribotag). We then used RNA sequencing to identify and quantify the astrocyte-enriched mRNA, analyzing 4 different brain regions: visual cortex, somatomotor cortex, hypothalamus, and cerebellum. Overall, we find that astrocyte expression of inflammatory and immune response factors increase with age, as well as changes in genes associated with metabolism, cholesterol synthesis, and synaptogenesis. Going forward, these data contribute to an understanding of astrocyte diversity and provide insight into the role of astrocytes in normal aging.
2017-12-11 | GSE99791 | GEO
Project description:Astrocytes, a major cell type found throughout the central nervous system have general roles in neuronal development, blood-brain barrier function, regulation of neuroimmune responses as well as metabolic support of other brain resident cells. Here we show that a distinct subtype of reactive astrocyte is induced by activated endothelial cells and is distinct from astrocytes classically activated by neuroinflammatory microglia. We show that activated endothelial cells strongly induce C3 + astrocytes that retain their phagocytic capacity while exhibiting a gain of neurotoxic function decreasing neuronal cell survival. We show that endothelial activated astrocytes have increased A1-astrocytic genes and exhibit a distinctive extracellular matrix remodeling profile. Finally, we show that endothelial activated astrocytes are Decorin positive and are associated to vascular amyloid deposits but not amyloid plaques in mouse models and AD/CAA patients. Taken together these findings show the existence of potentially extensive and subtle functional diversity of A1-reactive astrocytes. Astrocytes treated with Control or Activated Microglia or Endothelial Conditioned media
2022-03-18 | GSE180106 | GEO
Project description:MartínJiménez2017 - Genome-scale reconstruction of the human astrocyte metabolic network
This model is described in the article:
Genome-Scale Reconstruction
of the Human Astrocyte Metabolic Network.
Martín-Jiménez CA,
Salazar-Barreto D, Barreto GE, González J.
Front Aging Neurosci 2017; 9: 23
Abstract:
Astrocytes are the most abundant cells of the central
nervous system; they have a predominant role in maintaining
brain metabolism. In this sense, abnormal metabolic states have
been found in different neuropathological diseases.
Determination of metabolic states of astrocytes is difficult to
model using current experimental approaches given the high
number of reactions and metabolites present. Thus, genome-scale
metabolic networks derived from transcriptomic data can be used
as a framework to elucidate how astrocytes modulate human brain
metabolic states during normal conditions and in
neurodegenerative diseases. We performed a Genome-Scale
Reconstruction of the Human Astrocyte Metabolic Network with
the purpose of elucidating a significant portion of the
metabolic map of the astrocyte. This is the first global
high-quality, manually curated metabolic reconstruction network
of a human astrocyte. It includes 5,007 metabolites and 5,659
reactions distributed among 8 cell compartments,
(extracellular, cytoplasm, mitochondria, endoplasmic reticle,
Golgi apparatus, lysosome, peroxisome and nucleus). Using the
reconstructed network, the metabolic capabilities of human
astrocytes were calculated and compared both in normal and
ischemic conditions. We identified reactions activated in these
two states, which can be useful for understanding the
astrocytic pathways that are affected during brain disease.
Additionally, we also showed that the obtained flux
distributions in the model, are in accordance with
literature-based findings. Up to date, this is the most
complete representation of the human astrocyte in terms of
inclusion of genes, proteins, reactions and metabolic pathways,
being a useful guide for in-silico analysis of several
metabolic behaviors of the astrocyte during normal and
pathologic states.
This model is hosted on
BioModels Database
and identified by:
MODEL1608180000.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2017-05-18 | MODEL1608180000 | BioModels
Project description:Astrocytes are intimately linked with brain blood vessels, a relationship critical for neuronal function. However, astroglial factors driving these physical and functional associations during postnatal brain development have yet to be identified. By characterizing structural and transcriptional changes in mouse cortical astrocytes during the first two postnatal weeks, we find that high-mobility group box 1 (Hmgb1), normally upregulated with injury and involved in adult cerebrovascular repair, is highly expressed in astrocytes at birth and then decreases rapidly. Astrocyte-selective ablation of Hmgb1 at birth affects astrocyte morphology and endfoot placement, alters distribution of endfoot proteins connexin43 and aquaporin-4, induces transcriptional changes in astrocytes related to cytoskeleton remodeling, and profoundly disrupts endothelial ultrastructure. While lack of astroglial Hmgb1 does not affect the blood-brain barrier or angiogenesis postnatally, it impairs neurovascular coupling and behavior in adult mice. These findings identify astroglial Hmgb1 as a key player in postnatal gliovascular maturation.
2023-07-10 | GSE236429 | GEO
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