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| Status |
Public on Mar 15, 2018 |
| Title |
Dissecting the Functional Consequences of de Novo DNA Methylation Dynamics in Human Motor Neuron Differentiation and Physiology |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
DNA methylation is a well studied, yet still incompletely understood component of the multi-layered epigenome. The somatic DNA methylation landscape is established early in development, but remains highly dynamic within focal regions that tend to overlap with gene regulatory elements. The functional significance of these dynamic changes remains unresolved. Here we utilized a powerful human ESC differentiation model for the generation of motor neurons (MNs) in combination with genetic mutations in the de novo DNA methylation machinery to dissect the role of DNA methylation in directing somatic cell fate. We quantitatively and in high-resolution measure the molecular and functional consequences of epigenetic perturbation. We find defects in neuralization and MN development. We also observe decreased dendritic arborization and altered electrophysiological properties in DNMT3A KO MNs. Our work provides a specific list of epigenetically deregulated targets and a mechanistic link between de novo DNA methylation, cellular differentiation and human MN function.
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| Overall design |
We performed whole genome bisulfite sequencing and RNA-Seq on 3 time points during in vitro differentiation of human embryonic stem cells towards spinal motor neurons at day 0, day 6 and day 14 in three conditions, WT, DNMT3A and DNMT3B knockout backround in 3-5 replicates each. In addition, we also performed single cell RNA-Seq on the same conditions and time point 6 and 14 as well as bisulfite amplicon sequencing.
Please note that raw data is to be made available through dbGaP (controlled access) due to privacy concerns.
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| Contributor(s) |
Kiskinis E, Meissner A |
| Citation(s) |
29551301 |
| |
| Submission date |
Nov 26, 2016 |
| Last update date |
Mar 27, 2019 |
| Contact name |
Michael Johannes Ziller |
| Organization name |
Max Planck Institute of Psychiatry
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| Department |
Translational Psychiatry
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| Lab |
Ziller lab
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| Street address |
Kraepelinstrasse 2-10
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| City |
Munich |
| ZIP/Postal code |
80804 |
| Country |
Germany |
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| Platforms (4)
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| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL15520 |
Illumina MiSeq (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (100)
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| Relations |
| BioProject |
PRJNA355008 |
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