Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells
Summary: Induced pluripotent stem cells (iPSCs) are the foundation of cell therapy. Differences in gene expression, DNA methylation, and chromatin conformation, which could affect differentiation capacity, have been identified between iPSCs and embryonic stem cells (ESCs). Less is known about whethe...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723016753 |
| _version_ | 1827385728482410496 |
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| author | Matthew M. Edwards Ning Wang Dashiell J. Massey Sakshi Bhatele Dieter Egli Amnon Koren |
| author_facet | Matthew M. Edwards Ning Wang Dashiell J. Massey Sakshi Bhatele Dieter Egli Amnon Koren |
| author_sort | Matthew M. Edwards |
| collection | DOAJ |
| description | Summary: Induced pluripotent stem cells (iPSCs) are the foundation of cell therapy. Differences in gene expression, DNA methylation, and chromatin conformation, which could affect differentiation capacity, have been identified between iPSCs and embryonic stem cells (ESCs). Less is known about whether DNA replication timing, a process linked to both genome regulation and genome stability, is efficiently reprogrammed to the embryonic state. To answer this, we compare genome-wide replication timing between ESCs, iPSCs, and cells reprogrammed by somatic cell nuclear transfer (NT-ESCs). While NT-ESCs replicate their DNA in a manner indistinguishable from ESCs, a subset of iPSCs exhibits delayed replication at heterochromatic regions containing genes downregulated in iPSCs with incompletely reprogrammed DNA methylation. DNA replication delays are not the result of gene expression or DNA methylation aberrations and persist after cells differentiate to neuronal precursors. Thus, DNA replication timing can be resistant to reprogramming and influence the quality of iPSCs. |
| first_indexed | 2024-03-08T15:31:46Z |
| format | Article |
| id | doaj.art-91cd4c9d003a41d5a3af0ea2be01afdf |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-08T15:31:46Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-91cd4c9d003a41d5a3af0ea2be01afdf2024-01-10T04:36:01ZengElsevierCell Reports2211-12472024-01-01431113664Incomplete reprogramming of DNA replication timing in induced pluripotent stem cellsMatthew M. Edwards0Ning Wang1Dashiell J. Massey2Sakshi Bhatele3Dieter Egli4Amnon Koren5Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USADepartment of Pediatrics and Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA; Columbia University Stem Cell Initiative, New York, NY 10032, USADepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USADepartment of Pediatrics and Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA; Columbia University Stem Cell Initiative, New York, NY 10032, USADepartment of Pediatrics and Naomi Berrie Diabetes Center, Columbia University, New York, NY 10032, USA; Columbia University Stem Cell Initiative, New York, NY 10032, USA; Corresponding authorDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; Corresponding authorSummary: Induced pluripotent stem cells (iPSCs) are the foundation of cell therapy. Differences in gene expression, DNA methylation, and chromatin conformation, which could affect differentiation capacity, have been identified between iPSCs and embryonic stem cells (ESCs). Less is known about whether DNA replication timing, a process linked to both genome regulation and genome stability, is efficiently reprogrammed to the embryonic state. To answer this, we compare genome-wide replication timing between ESCs, iPSCs, and cells reprogrammed by somatic cell nuclear transfer (NT-ESCs). While NT-ESCs replicate their DNA in a manner indistinguishable from ESCs, a subset of iPSCs exhibits delayed replication at heterochromatic regions containing genes downregulated in iPSCs with incompletely reprogrammed DNA methylation. DNA replication delays are not the result of gene expression or DNA methylation aberrations and persist after cells differentiate to neuronal precursors. Thus, DNA replication timing can be resistant to reprogramming and influence the quality of iPSCs.http://www.sciencedirect.com/science/article/pii/S2211124723016753CP: Stem cell researchCP: Molecular biology |
| spellingShingle | Matthew M. Edwards Ning Wang Dashiell J. Massey Sakshi Bhatele Dieter Egli Amnon Koren Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells Cell Reports CP: Stem cell research CP: Molecular biology |
| title | Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells |
| title_full | Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells |
| title_fullStr | Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells |
| title_full_unstemmed | Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells |
| title_short | Incomplete reprogramming of DNA replication timing in induced pluripotent stem cells |
| title_sort | incomplete reprogramming of dna replication timing in induced pluripotent stem cells |
| topic | CP: Stem cell research CP: Molecular biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723016753 |
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