Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hmgb2 improves astrocyte to neuron conversion by increasing the chromatin accessibility of genes associated with neuronal maturation in a proneuronal factor-dependent manner [ATAC-Seq]

ABSTRACT: Direct conversion of reactive glial cells to neurons is promising avenue for the replacement therapies after brain injury or neurodegeneration. The overexpression of developmental neurogenic fate determinants in glial cells converts them to neurons. For the repair purposes the conversion is confined to the pathology-induced neuroinflammatory environment. However, very little is known about the influence of injury-induced neuroinflammatory environment on the direct conversion process. We established the new in vitro culture system of postnatal astrocytes that reflects the direct conversion rate in the injured, neuroinflammatory environment in vivo. We could show that the growth factor combination corresponding to the injured environment defines the capacity of the glia to be directly converted to neurons. Using this culture, we showed that the chromatin structural protein high mobility group b2 (Hmgb2) regulates the direct conversion rate downstream of the growth factor combination. We could further show that Hmgb2 cooperates with neurogenic fate determinants such as Neurog2 to open the chromatin containing neuronal maturation and synapse formation genes, leading to early chromatin re-arrangements during the direct fate conversion that are necessary for the full fate conversion. Our data demonstrate the novel, environmental cues controlled level of gene regulation during direct fate conversion necessary for the proper maturation of induced neurons that could be targeted to improve the repair process.

ORGANISM(S): Mus musculus

PROVIDER: GSE240782 | GEO | 2025/03/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hmgb2 improves astrocyte to neuron conversion by Neurog2-dependent increase in accessibility of genes related to neuronal maturation

Project description:Direct conversion of reactive glial cells to neurons is promising avenue for the replacement therapies after brain injury or neurodegeneration. The overexpression of developmental neurogenic fate determinants in glial cells converts them to neurons. For the repair purposes the conversion is confined to the pathology-induced neuroinflammatory environment. However, very little is known about the influence of injury-induced neuroinflammatory environment on the direct conversion process. We established the new in vitro culture system of postnatal astrocytes that reflects the direct conversion rate in the injured, neuroinflammatory environment in vivo. We could show that the growth factor combination corresponding to the injured environment defines the capacity of the glia to be directly converted to neurons. Using this culture, we showed that the chromatin structural protein high mobility group b2 (Hmgb2) regulate the direct conversion rate downstream of the growth factor combination. We could further show that Hmgb2 in cooperation with neurogenic fate determinants such as Neurog2 opens the chromatin containing neuronal maturation and synapse formation genes, leading to early chromatin re-arrangements during the direct fate conversion that are necessary for the full fate conversion. Our data demonstrate the novel, environmental cues controlled level of gene regulation during direct fate conversion necessary for the proper maturation of induced neurons that could be targeted to improve the repair process.

2025-03-06 | PXD044288 | Pride

Hmgb2 improves astrocyte to neuron conversion by increasing the chromatin accessibility of genes associated with neuronal maturation in a proneuronal factor-dependent manner[RNA-Seq]

Project description:Direct conversion of reactive glial cells to neurons is promising avenue for the replacement therapies after brain injury or neurodegeneration. The overexpression of developmental neurogenic fate determinants in glial cells converts them to neurons. For the repair purposes the conversion is confined to the pathology-induced neuroinflammatory environment. However, very little is known about the influence of injury-induced neuroinflammatory environment on the direct conversion process. We established the new in vitro culture system of postnatal astrocytes that reflects the direct conversion rate in the injured, neuroinflammatory environment in vivo. We could show that the growth factor combination corresponding to the injured environment defines the capacity of the glia to be directly converted to neurons. Using this culture, we showed that the chromatin structural protein high mobility group b2 (Hmgb2) regulates the direct conversion rate downstream of the growth factor combination. We could further show that Hmgb2 cooperates with neurogenic fate determinants such as Neurog2 to open the chromatin containing neuronal maturation and synapse formation genes, leading to early chromatin re-arrangements during the direct fate conversion that are necessary for the full fate conversion. Our data demonstrate the novel, environmental cues controlled level of gene regulation during direct fate conversion necessary for the proper maturation of induced neurons that could be targeted to improve the repair process.

2025-03-06 | GSE240857 | GEO

Identification of a core cross-regulatory neurogenic network regulated by the transcription factor Pax6 interacting with Brg1-containing SWI/SNF chromatin remodeling complex

Project description:The molecular mechanisms of neurogenic fate determination are of particular importance in light of the need to regenerate neurons. However the molecular logic of neurogenic fate determination is still ill understood, even though some key transcription factors have been implicated. Here we describe how one of these, the transcription factor Pax6, regulates adult neurogenesis by initiating a cross-regulatory network of 3 transcription factors executing neuronal fate and regulating genes required for neuronal differentiation. This network is initiated and driven to sufficiently high expression levels by the transcription factor Pax6 in close interaction with Brg1-containing SWI/SNF chromatin remodeling factors. Genetic deletion of either Pax6 or Brg1, the ATPase unit of the SWI/SNF complex, in neural stem cells of the adult mouse subependymal zone results in a fate conversion to distinct glial subtypes most pronounced when neuroblasts leave the neurogenic niche. Consistent with the phenocopy in vivo virtually all genes down-regulated by Brg1 deletion have Pax6-binding motifs. Amongst the few down-stream transcription factors are Sox11, Nfib and Brn4 that crossregulate each other and rescue neurogenesis also in direct reprogramming in the absence of Brg1 (or Pax6). Thus the function of Pax6-SWI/SNF is necessary and sufficient for neuronal fate maintenance and initiates a cross-regulatory effector network required for neuronal fate execution and maintenance to counteract glial differentiation in the adult brain. This identifies a novel role highly specific role of a chromatin-remodelling complex in stabilizing fate decisions in normal and forced neurogenesis. We performed gene expression microarray analysis on tissue derived from the SEZ or from the core region of the olfactory bulb from Brg1 cKO and control mice

2013-08-01 | E-GEOD-39362 | biostudies-arrayexpress

Identification of a core cross-regulatory neurogenic network regulated by the transcription factor Pax6 interacting with Brg1-containing SWI/SNF chromatin remodeling complex

2013-08-01 | GSE39362 | GEO

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs II

Project description:Neurogenic microRNAs 9/9* and 124 (miR-9/9*-124) drive the direct reprogramming of human fibroblasts into neurons with the initiation of the fate erasure of fibroblasts. However, whether the miR-9/9*-124 fate erasure logic extends to neuronal conversion of other somatic cell types remains unknown. Here, we uncover that miR-9/9*-124 induce neuronal conversion of multiple cell types: dura fibroblasts, astrocytes, smooth muscle cells, and pericytes. We reveal the cell type-specific and pan-somatic gene network erasure induced by miR-9/9*-124, including cell cycle, morphology, and proteostasis gene networks. Leveraging these pan-somatic gene networks, we predict upstream regulators that may antagonize somatic fate erasure. Among the predicted regulators, we identify TP53 (p53) whose inhibition is sufficient to enhance neuronal conversion even in post-mitotic cells. This study extends miR-9/9*-124 reprogramming to alternate somatic cells, reveals the pan-somatic gene network fate erasure logic of miR-9/9*-124, and shows a neurogenic role for p53-inhibition in the miR-9/9*-124-signaling cascade.

2024-12-31 | GSE283006 | GEO

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs I

2024-12-31 | GSE283004 | GEO

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs IV

2024-12-31 | GSE283009 | GEO

Fate Erasure Logic of Gene Networks Underlying Direct Neuronal Conversion of Somatic Cells by MicroRNAs III

2024-12-31 | GSE283008 | GEO

Transcriptome profiling of microRNA-induced neurons, microRNA-induced motor neurons, and starting fibroblasts [array]

Project description:Neuronal microRNAs miR-9/9* and miR-124 (miR-9/9*-124) direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and work in concert with additional transcription factors to enable the generation of discrete neuronal subtypes. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone. We found that miR-9/9*-124 surprisingly stimulate reconfiguration of chromatin accessibility, DNA methylation and mRNA levels, leading to the generation of functionally excitable neurons that are not yet biased towards a particular subtype-lineage. Further subtype identity can be programmed through additional transcription factors. As such, we show ISL1 and LHX3 selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons.

2017-08-04 | GSE102034 | GEO

Transcriptome profiling at day 30 of microRNA-mediated neuronal reprogramming [RNA-seq d30]

Project description:Neuronal microRNAs, miR-9/9* and miR-124 (miR-9/9*-124), exert reprogramming activities to direct cell-fate conversion of adult human fibroblasts to post-mitotic neurons and enable the generation of discrete neuronal subtypes with additional transcription factors. Previously, the molecular events underlying the neurogenic switch mediated by microRNAs during neuronal reprogramming were unknown. Here, we systematically dissected the neurogenic state induced by miR-9/9*-124 alone and reveal the surprising capability of miR-9/9*-124 in coordinately stimulating the reconfiguration of chromatin accessibilities, DNA methylation and transcriptome, leading to the generation of functionally excitable neurons, yet unbiased towards a particular subtype-lineage. We show that the microRNA-induced neuronal state enables additional transcription factors, ISL1 and LHX3, to selectively commit conversion to a highly homogenous population of human spinal cord motor neurons. Taken together, our study reveals a modular synergism between microRNAs and transcription factors that allows lineage-specific neuronal reprogramming, providing a platform for generating distinct subtypes of human neurons.

2017-08-04 | GSE102033 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data