Decoding transcriptional identity during Neuron-Astroglia Cell Fate driven by RAR-specific agonists [Spatial transcriptomics]
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PROVIDER: PRJNA1208474 | ENA |
REPOSITORIES: ENA
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Project description:Decoding transcriptional identity during Neuron-Astroglia Cell Fate driven by RAR-specific agonists [CUT&Tag]
| PRJNA1208478 | ENA
Project description:Decoding transcriptional identity during Neuron-Astroglia Cell Fate driven by RAR-specific agonists [scRNA-seq]
| PRJNA1208486 | ENA
Project description:How cells respond to different signals leading to defined lineages is an open question to understand physiological differentiation leading to the formation of organs and tissues. Among the various morphogens, retinoic acid signaling, via the RXR/RAR nuclear receptors activation, is a key morphogen of nervous system development and brain homeostasis. Here we analyze gene expression in ~80,000 cells covering 16 days of monolayer mouse stem cell differentiation driven by the pan-RAR agonist all-trans retinoic acid, the RAR-alpha agonist BMS753 or the activation of both RAR-beta and RAR-gamma receptors (BMS641+BMS961). Furthermore, we have elucidated the role of these retinoids for driving nervous tissue formation within 90 days of brain organoid cultures, by analyzing > 8,000 distinct spatial regions over 28 brain organoids. Despite a delayed progression in BMS641+BMS961, RAR-specific agonists led to a variety of neuronal subtypes, astrocytes and oligodendrocyte precursors. Spatially-resolved transcriptomics performed in organoids revealed spatially distinct RAR isotype expression leading to specialization signatures associated to matured tissues, including a variety of neuronal subtypes, retina-like tissue structure signatures and even the presence of microglia.
2025-01-13 | GSE286249 | GEO
Project description:How cells respond to different signals leading to defined lineages is an open question to understand physiological differentiation leading to the formation of organs and tissues. Among the various morphogens, retinoic acid signaling, via the RXR/RAR nuclear receptors activation, is a key morphogen of nervous system development and brain homeostasis. Here we analyze gene expression in ~80,000 cells covering 16 days of monolayer mouse stem cell differentiation driven by the pan-RAR agonist all-trans retinoic acid, the RAR-alpha agonist BMS753 or the activation of both RAR-beta and RAR-gamma receptors (BMS641+BMS961). Furthermore, we have elucidated the role of these retinoids for driving nervous tissue formation within 90 days of brain organoid cultures, by analyzing > 8,000 distinct spatial regions over 28 brain organoids. Despite a delayed progression in BMS641+BMS961, RAR-specific agonists led to a variety of neuronal subtypes, astrocytes and oligodendrocyte precursors. Spatially-resolved transcriptomics performed in organoids revealed spatially distinct RAR isotype expression leading to specialization signatures associated to matured tissues, including a variety of neuronal subtypes, retina-like tissue structure signatures and even the presence of microglia.
2025-01-13 | GSE286245 | GEO
Project description:How cells respond to different signals leading to defined lineages is an open question to understand physiological differentiation leading to the formation of organs and tissues. Among the various morphogens, retinoic acid signaling, via the RXR/RAR nuclear receptors activation, is a key morphogen of nervous system development and brain homeostasis. Here we analyze gene expression in ~80,000 cells covering 16 days of monolayer mouse stem cell differentiation driven by the pan-RAR agonist all-trans retinoic acid, the RAR-alpha agonist BMS753 or the activation of both RAR-beta and RAR-gamma receptors (BMS641+BMS961). Furthermore, we have elucidated the role of these retinoids for driving nervous tissue formation within 90 days of brain organoid cultures, by analyzing > 8,000 distinct spatial regions over 28 brain organoids. Despite a delayed progression in BMS641+BMS961, RAR-specific agonists led to a variety of neuronal subtypes, astrocytes and oligodendrocyte precursors. Spatially-resolved transcriptomics performed in organoids revealed spatially distinct RAR isotype expression leading to specialization signatures associated to matured tissues, including a variety of neuronal subtypes, retina-like tissue structure signatures and even the presence of microglia.
2025-01-13 | GSE286250 | GEO
Project description:Astroglia are integral to brain development and the emergence of neurodevelopmental disorders. However, studying the pathophysiology of human astroglia using brain organoid models has been hindered by inefficient astrogliogenesis. In this study, we introduce a robust method for generating astroglia-enriched organoids through BMP4 treatment during the neural differentiation phase of organoid development. Our RNA sequencing analysis reveals that astroglia developed within these organoids exhibit advanced developmental characteristics and enhanced synaptic functions compared to those grown under traditional two-dimensional conditions, particularly highlighted by increased neurexin (NRXN)-neuroligin (NLGN) signaling. Cell adhesion molecules, such as NRXN and NLGN, are essential in regulating interactions between astroglia and neurons. We further discovered that brain organoids derived from human embryonic stem cells (hESCs) harboring the autism-associated NLGN3 R451C mutation exhibit increased astrogliogenesis. Notably, the NLGN3 R451C astroglia demonstrate enhanced branching, indicating a more intricate morphology. Interestingly, our RNA sequencing data suggest that these mutant astroglia significantly upregulate pathways that support neural functions when compared to isogenic wild-type astroglia. Our findings establish a novel astroglia-enriched organoid model, offering a valuable platform for probing the roles of human astroglia in brain development and related disorders.
2024-12-08 | GSE283484 | GEO
Project description:Astroglia are the most abundant cell type in the central nervous system. They play essential roles in the homeostasis of the CNS. Astroglia are extremely diverse. In Amyotrophic Lateral Sclerosis (ALS) astroglia in spinal cord undergo dramatic transcriptomic dysregulation. However there is little to no data on the effects that cortical astroglia undergo during ALS pathogenesis. In this study we isolated pure cortical astroglia in end stage ALS mice. We performed microarray analysis and discovered dysregulated pathways and genetic markers. This may serve as a database for scientists to understand the effects that abnormal cortical astroglia have on cortical motor neurons and overall ALS pathology.
2019-04-30 | GSE111031 | GEO
Project description:Neurogenesis is limited in mammalian brains and Alzheimer’s disease conditions further reduce the neurogenic output. Recent findings suggest that reduced neurogenesis could be one of the reasons underlying the exacerbated neuropathology in humans, and restoring the neural stem cell proliferation and neurogenesis could help circumventing some pathological aspects of Alzheimer’s disease. We recently identified Interleukin-4/STAT6 signaling as a neuron-glia crosstalk mechanism that enables glial proliferation and neurogenesis in adult zebrafish brain and 3D cultures of human astroglia, which manifest neurogenic properties. In this study, we tested whether activating IL4/STAT6 signaling in adult mouse astroglia would enhance cell proliferation and neurogenesis in health and disease conditions. By using single cell sequencing in APP/PS1dE9 mouse model of AD, we found that IL4 receptor (Il4r) is not expressed in mouse astroglia. Lentivirus-mediated expression of IL4R or constitutively active STAT6V impaired the survival capacity of mouse astroglia in vivo but not in vitro. Our findings suggest that adult mouse brain generates a non-permissive environment that dictates a negative effect of IL4 signaling on astroglial survival and neurogenic properties in contrast to zebrafish brains and in vitro mammalian cell cultures.
2020-03-23 | GSE140793 | GEO
Project description:Retinoic Acid Receptors (RARs) as a functional heterodimer with Retinoid X Receptors (RXRs), bind a diverse series of RA-response elements (RAREs) in regulated genes. Among them, the non-canonical DR0 elements are bound by RXR-RAR with comparable affinities to DR5 elements but DR0 elements do not act transcriptionally as independent RAREs. In this work, we present structural insight for the recognition of DR5 and DR0 elements by RXR-RAR heterodimer using x-ray crystallography, small angle x-ray scattering, and hydrogen/deuterium exchange coupled to mass spectrometry. We solved the crystal structure of RXR-RAR DNA-binding domain in complex with the Rarb2 DR5 and RXR DNA-binding domain in complex with Hoxb13 DR0. While cooperative binding was observed on DR5, on DR0 the two molecules bound non-cooperatively on opposite sides of the DNA. In addition, our data unveil the structural organization and dynamics of the multi-domain RXR-RAR DNA complexes providing evidence for DNA-dependent allosteric communication between domains. Differential binding mode between DR0 and DR5 were observed leading to differences in the conformation and structural dynamics of the multi-domain RXR-RAR DNA complex. These results reveal that the topological organization of the RAR binding element confer regulatory information by modulating the overall topology and structural dynamics of the RXR-RAR heterodimers.
2021-02-10 | PXD018172 | Pride
Project description:Percellome analysis of whole Xenopus embryos at developmental stage 18 Xenopus embryos were treated with TTNPB (RAR-agonist), AGN193109 (RAR-antagonist), or Control Vehicle at Nieuwkoop and Faber Stage 7. Embryos were collected at stage 18, followed by RNA extraction, hybridization on Affymetrix microarrays, and Percellome analysis.
2014-05-06 | E-GEOD-57352 | biostudies-arrayexpress