Projects per year
Abstract
DNA methylation in neurons is directly linked to neuronal genome regulation and maturation. Unlike other tissues, vertebrate neurons accumulate high levels of atypical DNA methylation in the CH sequence context (mCH) during early postnatal brain development. Here, we investigate to what extent neurons derived in vitro from both mouse and human pluripotent stem cells recapitulate in vivo DNA methylation patterns. While human ESC-derived neurons did not accumulate mCH in either 2D culture or 3D organoid models even after prolonged culture, cortical neurons derived from mouse ESCs acquired in vivo levels of mCH over a similar time period in both primary neuron cultures and in vivo development. mESC-derived neuron mCH deposition was coincident with a transient increase in Dnmt3a, preceded by the postmitotic marker Rbfox3 (NeuN), was enriched at the nuclear lamina, and negatively correlated with gene expression. We further found that methylation patterning subtly differed between in vitro mES-derived and in vivo neurons, suggesting the involvement of additional noncell autonomous processes. Our findings show that mouse ESC-derived neurons, in contrast to those of humans, can recapitulate the unique DNA methylation landscape of adult neurons in vitro over experimentally tractable timeframes, which allows their use as a model system to study epigenome maturation over development.
Original language | English |
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Article number | 957 |
Journal | Genes |
Volume | 14 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2023 |
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Embryonic stem cell-derived neurons as a model system for epigenome maturation during development
Martin, S. (Creator), Poppe, D. (Creator), Olova, N. (Creator), O'Leary, C. (Creator), Ivanova, E. (Creator), Pflueger, J. (Creator), Dechka, J. (Creator), Simmons, R. (Creator), Cooper, H. M. (Creator), Reik, W. (Creator), Lister, R. (Creator) & Wolvetang, E. (Creator), Gene Expression Omnibus (NCBI), 25 Jul 2023
DOI: 10.26182/1gxr-k908, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137098
Dataset
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Leveraging genomics strategies to generate adult neurons from iPSCs and somatic cells
Lister, R., Polo, J., Wolvetang, E. & Heng, J.
NHMRC National Health and Medical Research Council
1/01/17 → 31/12/20
Project: Research
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Deciphering the role of atypical DNA methylation in neural genome regulation and neurological disorders
Lister, R., Wolvetang, E. & Bogdanovic, O.
NHMRC National Health and Medical Research Council
1/01/15 → 31/12/17
Project: Research