NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE151818 Query DataSets for GSE151818
Status Public on Apr 27, 2021
Title 5-hydroxymethylcytosine is Dynamically Regulated During Forebrain Organoid Development and Prematurely Altered in Forebrain Organoids of Alzheimer’s Disease Patients
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary 5-hydroxymethylcytosine (5hmC) endures dynamic changes during mammalian brain development and its aberrant regulation is known to be associated with numerous neurological diseases such as Alzheimer’s Disease (AD). Recent evidence suggests that key epigenetic changes could occur during neural development long before the onset of neurodegenerative disorders. However, the dynamics of 5hmC during early human brain development and how that contributes to pathogenesis of neurodegeneration, particularly AD pathologies, remain largely unexplored. To investigate this, we utilized the human iPSC-derived organoid model. We derived the 5hmC and transcriptome profiles across healthy forebrain-organoid developmental time points, as well as a patient derived AD organoid time point, allowing us to study brain development at the cellular and molecular levels. In the present study, we identified stage specific differentially hydroxymethylated regions that demonstrated unique acquisition and depletion of 5hmC modifications across development stages. In addition, genes bearing concomitant increases or decreases in both 5hmC and gene expression were enriched in neurobiological processes or early developmental processes respectively. Our AD organoids corroborate both cellular and epigenetic phenotypes previously observed in human AD brains. Importantly, in AD organoids, we identified significant 5hmC alterations at key neurodevelopmental and AD-risk genes, consequently downregulating genes involved in neurodevelopmental and immune response pathways. Collectively our data indicates that, during human fetal neurodevelopment, the precise temporal regulation of 5hmC could modulate key gene expression patterns ensuring that critical neurodevelopmental milestones are achieved. Further, we also demonstrate that premature epigenetic dysregulation of the 5hmC landscape during neuronal development may predispose AD pathogenesis.
 
Overall design Examine the dynamics of 5hmC during early human brain development and how alterations in those dynamics may contribute to Alzheimer's Disease
 
Contributor(s) Kuehner JN, Chen J
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Jun 04, 2020
Last update date May 01, 2021
Contact name Janise Nichole Kuehner
E-mail(s) janise.nichole.unger@emory.edu
Organization name Emory University
Department Human Genetics
Lab Bing Yao
Street address 615 Michael St NE
City Atlanta
State/province GA
ZIP/Postal code 30322
Country USA
 
Platforms (1)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
Samples (48)
GSM4591389 EB_4
GSM4591390 EB_5
GSM4591391 D56_1
Relations
BioProject PRJNA637330
SRA SRP265976

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE151818_CtrlvsAD_Down.bed.gz 136.8 Kb (ftp)(http) BED
GSE151818_CtrlvsAD_Up.bed.gz 79.9 Kb (ftp)(http) BED
GSE151818_D56vsD84.Down.bed.gz 67.0 Kb (ftp)(http) BED
GSE151818_D56vsD84.Up.bed.gz 115.4 Kb (ftp)(http) BED
GSE151818_D56vsDD84.gene_exp.diff.gz 884.4 Kb (ftp)(http) DIFF
GSE151818_D84vsAD.gene_exp.diff.gz 841.4 Kb (ftp)(http) DIFF
GSE151818_D84vsD112.Down.bed.gz 124.0 Kb (ftp)(http) BED
GSE151818_D84vsD112.Up.bed.gz 83.0 Kb (ftp)(http) BED
GSE151818_D84vsD112.gene_exp.diff.gz 865.0 Kb (ftp)(http) DIFF
GSE151818_EBvsD56.Down.bed.gz 392.1 Kb (ftp)(http) BED
GSE151818_EBvsD56.Up.bed.gz 143.2 Kb (ftp)(http) BED
GSE151818_EBvsD56.gene_exp.diff.gz 889.2 Kb (ftp)(http) DIFF
GSE151818_RAW.tar 79.3 Mb (http)(custom) TAR (of NARROWPEAK)
SRA Run SelectorHelp
Processed data provided as supplementary file
Processed data are available on Series record
Raw data are available in SRA

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap
External link. Please review our privacy policy.