Incomplete DNA methylation underlies a transcriptional memory of the somatic cell in human iPS cells
By Y. Ohi, Han Qin, C. Hong, L. Blouin, J. Polo, Tingxi Guo, Zhongxia Qi, Sara L. Downey, Philip D. Manos, Derrick J. Rossi and 6 more. Nature Cell Biology, 2011
595 citations recorded by the source corpus.
Human induced pluripotent stem (iPS) cells are remarkably similar to embryonic stem (ES) cells, but recent reports indicate that there may be important differences between them. We carried out a systematic comparison of human iPS cells generated from hepatocytes (representative of endoderm), skin fibroblasts (mesoderm) and melanocytes (ectoderm). All low-passage iPS cells analysed retain a transcriptional memory of the original cells. The persistent expression of somatic genes can be partially explained by incomplete promoter DNA methylation. This epigenetic mechanism underlies a robust form of memory that can be found in iPS cells generated by multiple laboratories using different methods, including RNA transfection. Incompletely silenced genes tend to be isolated from other genes that are repressed during reprogramming, indicating that recruitment of the silencing machinery may be inefficient at isolated genes. Knockdown of the incompletely reprogrammed gene C9orf64 (chromosome 9 open reading frame 64) reduces the efficiency of human iPS cell generation, indicating that somatic memory genes may be functionally relevant during reprogramming.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/7b9414b42265c253f62e6bf30780410b87921d80
Citations in the corpus
- Production of De Novo Cardiomyocytes: Human Pluripotent Stem Cell Differentiation and Direct Reprogramming (2012, unknown): “, 2010), but recent data suggest that this effect is maintained in later passages as well (Ohi et al., 2011).”
- Epigenetic memory and preferential lineage-specific differentiation in induced pluripotent stem cells derived from human pancreatic islet beta cells. (2011, unknown): “Some emerging works also show a unique DNA methylation signature that is inherited from a parental human cell following reprogramming (Doi et al., 2009; Lister et al., 2011; Ohi et al., 2011).”
- Induced pluripotent stem cells: past, present, and future. (2012, unknown): “…making progress toward using iPSCs in regenerative medicine, for example for the treatment of Parkinson’s disease (Kriks et al., 2011), platelet deficiency (Takayama et al., 2010), spinal cord injury (Nori et al., 2011; Tsuji et al., 2010), and macular degeneration (Okamoto and Takahashi, 2011).”