Reactivation of the inactive X chromosome and post-transcriptional reprogramming of Xist in iPSCs.
Direct reprogramming of somatic cells to pluripotent stem cells entails the obliteration of somatic cell memory and the reestablishment of epigenetic events. Induced pluripotent stem cells (iPSCs) have been created by reprogramming somatic cells through the transduction of reprogramming factors. During cell reprogramming, female somatic cells must overcome at least one more barrier than male somatic cells in order to enter a pluripotent state, as they must reactivate an inactive X chromosome (Xi). In this study, we investigated whether the sex of somatic cells affects reprogramming efficiency, differentiation potential and the post-transcriptional processing of Xist RNA after reprogramming. There were no differences between male and female iPSCs with respect to reprogramming efficiency or their differentiation potential in vivo. However, reactivating Xi took longer than reactivating pluripotency-related genes. We also found that direct reprogramming leads to gender-appropriate post-transcriptional reprogramming - like male embryonic stem cells (ESCs), male iPSCs expressed only the long Xist isoform, whereas female iPSCs, like female ESCs, expressed both the long and short isoforms.
Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 133-702, Republic of Korea.
Jong Soo
JS
Kim
Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 133-702, Republic of Korea.
Hyun Woo
HW
Choi
Group of Computational Biology and Systems Biomedicine, Biodonostia Health Research Institute, San Sebastian 20014, Spain IKERBASQUE, Basque Foundation for Science, Bilbao 48013, Spain.
Marcos J
MJ
Araúzo-Bravo
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Röntgenstrasse 20, Münster 48149, Germany.
Hans R
HR
Schöler
Department of Animal Biotechnology, College of Animal Bioscience and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 133-702, Republic of Korea dojt@konkuk.ac.kr.
Jeong Tae
JT
Do
D000818:Animals; D065150:Cellular Reprogramming; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D012727:Sex Characteristics; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism*; D049951:X Chromosome Inactivation
D062085:RNA, Long Noncoding; C077885:XIST non-coding RNA
Oct4; Pluripotency; Reprogramming; Xist isoform; iPSC