Reprogramming of Xist against the pluripotent state in fusion hybrids.
The fusion of somatic cells with pluripotent cells results in the generation of pluripotent hybrid cells. Because the ;memory' of somatic cells seems to be erased during fusion-induced reprogramming, genetic reprogramming is thought to be a largely unidirectional process. Here we show that fusion-induced reprogramming, which brings about the formation of pluripotent hybrids, does not always follow a unidirectional route. Xist is a unique gene in that it is reprogrammed to the state of somatic cells in fusion-induced pluripotent hybrids. In hybrids formed from the cell fusion of embryonal carcinoma cells (ECCs) with male neural stem cells (mNSCs), the Xist gene was found to be reprogrammed to the somatic cell state, whereas the pluripotency-related and tissue-specific marker genes were reprogrammed to the pluripotent cell state. Specifically, Xist is not expressed in hybrids, because the ;memory' of the somatic cell has been retained (i.e. mNSCs do not exhibit Xist expression) and that of the pluripotent cell erased (i.e. inactivation of the partially active Xist gene of ECCs, complete methylation of the Xist region). The latter phenomenon is induced by male, but not by female, NSCs.
Do
Jeong Tae
JT
CHA Stem Cell Institute, CHA University, Gangnam-gu, Seoul 135-081, Korea. dojt@cha.ac.kr
Han
Dong Wook
DW
Gentile
Luca
L
Sobek-Klocke
Ingeborg
I
Wutz
Anton
A
Schöler
Hans R
HR
D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication; D002459:Cell Fusion; D002460:Cell Line; D065150:Cellular Reprogramming / Q000235:genetics*; D019175:DNA Methylation; D054278:Embryonal Carcinoma Stem Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006822:Hybrid Cells / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics* / Q000378:metabolism*; D012737:Sex Factors
D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA