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Genomic Imprinting Change by Reprogramming and Re‐differentiation

  • 언어ENG
  • URLhttps://db.koreascholar.com/Article/Detail/213395
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한국동물번식학회 (The Korean Society of Animal Reproduction)
초록

Induced pluripotent stem cells (iPSCs), generated by the overexpression of transcription factors Oct4, Sox2, Klf4 and c‐Myc in somatic cells, are pluripotent. iPSCs reprogrammed from differentiated cells get through a epigenetic modification during reprogramming and finally have the similar epigenetic state to embryonic stem cells (ESCs). In this study, these epigenetic changes were observed in reprogramming of uni‐parental parthenogenetic somatic cells. Furthermore, we have shown that parthenogenetic pattern of imprinted genes were changed during pluripotential reprogramming. Parthenogenetic neural stem cells (pNSCs) containing only maternal alleles regain the biparental imprinting patterns after reprogramming. However, we have yet to define whether the changed imprinted genes are maintained or reverted to the parthenogenetic state when the reprogrammed cells are differentiated into specialized cell types. To address this question, we compared genome‐wide expression profiles of biparental female neural stem cells (fNSCs), parthenogenetic neural stem cells (pNSCs), and NSCs differentiated from parthenogenetic maternal iPSC (miPS‐NSCs). Furthermore, this study establishes the correlation between the alteration of genome methylation and activation of imprinting genes in the parthenogenetic cells and reports for the first time that the silenced PWS‐related imprinted genes are activated in miPS‐NSCs. Our data demonstrated that pluripotential reprogramming of parthenogenetic somatic cells were able to reset the parthenogenetic imprinting patterns; reprogrammed miPSCs showed erasure of maternal methylation imprints and acquisition of methylation in paternally imprinted genes. Furthermore, the changed imprinting patterns were maintained when the reprogrammed cells are differentiated into specialized cell type. * This work was supported by the Next‐Generation BioGreen 21 program (Grant PJ008- 009) funded by the Rural Development Administration, Republic of Korea.

저자
  • Min Jung Kim(Laboratory of Stem Cell and Developmental Biology, CHA University, Seoul 135‐081, Republic of Korea)
  • Hyun Woo Choi(Laboratory of Stem Cell and Developmental Biology, CHA University, Seoul 135‐081, Republic of Korea)
  • Sol Choi(Laboratory of Stem Cell and Developmental Biology, CHA University, Seoul 135‐081, Republic of Korea)
  • Hyung Min Chung(dCHA Bio & Diostech Col, Ltd., Seoul Republic of Korea)
  • Jeong Tae Do(Laboratory of Stem Cell and Developmental Biology, CHA University, Seoul 135‐081, Republic of Korea)