DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling
Abstract Background Genetic predisposition and epigenetic alterations are both considered to contribute to sporadic neurodegenerative diseases (NDDs) such as Parkinson’s disease (PD). Since cell reprogramming and the generation of induced pluripotent stem cells (iPSCs) are themselves associated with...
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| Format: | Article |
| Language: | English |
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BMC
2018-01-01
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| Series: | Clinical Epigenetics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13148-018-0440-0 |
| _version_ | 1818056829432758272 |
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| author | Laura de Boni Gilles Gasparoni Carolin Haubenreich Sascha Tierling Ina Schmitt Michael Peitz Philipp Koch Jörn Walter Ullrich Wüllner Oliver Brüstle |
| author_facet | Laura de Boni Gilles Gasparoni Carolin Haubenreich Sascha Tierling Ina Schmitt Michael Peitz Philipp Koch Jörn Walter Ullrich Wüllner Oliver Brüstle |
| author_sort | Laura de Boni |
| collection | DOAJ |
| description | Abstract Background Genetic predisposition and epigenetic alterations are both considered to contribute to sporadic neurodegenerative diseases (NDDs) such as Parkinson’s disease (PD). Since cell reprogramming and the generation of induced pluripotent stem cells (iPSCs) are themselves associated with major epigenetic remodeling, it remains unclear to what extent iPSC-derived neurons lend themselves to model epigenetic disease-associated changes. A key question to be addressed in this context is whether iPSC-derived neurons exhibit epigenetic signatures typically observed in neurons derived from non-reprogrammed human embryonic stem cells (hESCs). Results Here, we compare mature neurons derived from hESC and isogenic human iPSC generated from hESC-derived neural stem cells. Genome-wide 450 K-based DNA methylation and HT12v4 gene array expression analyses were complemented by a deep analysis of selected genes known to be involved in NDD. Our studies show that DNA methylation and gene expression patterns of isogenic hESC- and iPSC-derived neurons are markedly preserved on a genome-wide and single gene level. Conclusions Overall, iPSC-derived neurons exhibit similar DNA methylation patterns compared to isogenic hESC-derived neurons. Further studies will be required to explore whether the epigenetic patterns observed in iPSC-derived neurons correspond to those detectable in native brain neurons. |
| first_indexed | 2024-12-10T12:35:03Z |
| format | Article |
| id | doaj.art-2a2e04b8e2dc4a00914a789f99f6d1fa |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-12-10T12:35:03Z |
| publishDate | 2018-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-2a2e04b8e2dc4a00914a789f99f6d1fa2022-12-22T01:48:40ZengBMCClinical Epigenetics1868-70751868-70832018-01-0110111310.1186/s13148-018-0440-0DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modelingLaura de Boni0Gilles Gasparoni1Carolin Haubenreich2Sascha Tierling3Ina Schmitt4Michael Peitz5Philipp Koch6Jörn Walter7Ullrich Wüllner8Oliver Brüstle9Department of Neurology, University Hospital of BonnInstitute for Genetics/Epigenetics, FR8.3 Life Sciences, Saarland UniversityInstitute of Reconstructive Neurobiology, Life & Brain Center, University of BonnInstitute for Genetics/Epigenetics, FR8.3 Life Sciences, Saarland UniversityDepartment of Neurology, University Hospital of BonnInstitute of Reconstructive Neurobiology, Life & Brain Center, University of BonnInstitute of Reconstructive Neurobiology, Life & Brain Center, University of BonnInstitute for Genetics/Epigenetics, FR8.3 Life Sciences, Saarland UniversityDepartment of Neurology, University Hospital of BonnInstitute of Reconstructive Neurobiology, Life & Brain Center, University of BonnAbstract Background Genetic predisposition and epigenetic alterations are both considered to contribute to sporadic neurodegenerative diseases (NDDs) such as Parkinson’s disease (PD). Since cell reprogramming and the generation of induced pluripotent stem cells (iPSCs) are themselves associated with major epigenetic remodeling, it remains unclear to what extent iPSC-derived neurons lend themselves to model epigenetic disease-associated changes. A key question to be addressed in this context is whether iPSC-derived neurons exhibit epigenetic signatures typically observed in neurons derived from non-reprogrammed human embryonic stem cells (hESCs). Results Here, we compare mature neurons derived from hESC and isogenic human iPSC generated from hESC-derived neural stem cells. Genome-wide 450 K-based DNA methylation and HT12v4 gene array expression analyses were complemented by a deep analysis of selected genes known to be involved in NDD. Our studies show that DNA methylation and gene expression patterns of isogenic hESC- and iPSC-derived neurons are markedly preserved on a genome-wide and single gene level. Conclusions Overall, iPSC-derived neurons exhibit similar DNA methylation patterns compared to isogenic hESC-derived neurons. Further studies will be required to explore whether the epigenetic patterns observed in iPSC-derived neurons correspond to those detectable in native brain neurons.http://link.springer.com/article/10.1186/s13148-018-0440-0DNA methylationIsogenic stem cellsiPS cell-derived neurons |
| spellingShingle | Laura de Boni Gilles Gasparoni Carolin Haubenreich Sascha Tierling Ina Schmitt Michael Peitz Philipp Koch Jörn Walter Ullrich Wüllner Oliver Brüstle DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling Clinical Epigenetics DNA methylation Isogenic stem cells iPS cell-derived neurons |
| title | DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling |
| title_full | DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling |
| title_fullStr | DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling |
| title_full_unstemmed | DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling |
| title_short | DNA methylation alterations in iPSC- and hESC-derived neurons: potential implications for neurological disease modeling |
| title_sort | dna methylation alterations in ipsc and hesc derived neurons potential implications for neurological disease modeling |
| topic | DNA methylation Isogenic stem cells iPS cell-derived neurons |
| url | http://link.springer.com/article/10.1186/s13148-018-0440-0 |
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