Erasure of cellular memory by fusion with pluripotent cells.
Pluripotent cells have been suggested as a prime source to reprogram somatic cells. We used F9 EC cells as a pluripotent partner to reprogram neurosphere cells (NSCs) because they exhibit a nonneural differentiation potential in the presence of retinoic acid. F9-NSC hybrid cells displayed various features of reprogramming, such as reactivation of pluripotency genes, inactivation of tissue-specific genes, and reactivation of the inactive X chromosome. As the hybrid cells undergo differentiation, the pluripotency markers Oct4 and Nanog were downregulated. Whereas neural marker genes were not upregulated, endodermal and mesodermal markers were, suggesting that NSCs lose memory of their neural origin and preferentially differentiate to the lineages corresponding to the F9 program. After fusion, the methylation status in the Xist region was similar to that of F9 EC cells. However, upon differentiation, the Xist region failed to resume the methylation patterns of differentiated cells, suggesting that the Xist in F9-NSC hybrids does not easily acquire a differentiated state.
Do
Jeong Tae
JT
Department of Cell and Developmental Biology, Max Planck Institute for Molecular Biomedicine, Münster, Germany.
Han
Dong Wook
DW
Gentile
Luca
L
Sobek-Klocke
Ingeborg
I
Stehling
Martin
M
Lee
Hoon Taek
HT
Schöler
Hans R
HR
D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D002455:Cell Division; D002459:Cell Fusion; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000502:physiology; D004622:Embryo, Mammalian; D005260:Female; D006822:Hybrid Cells / Q000166:cytology* / Q000502:physiology*; D007621:Karyotyping; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000502:physiology; D010053:Ovary / Q000166:cytology / Q000196:embryology / Q000502:physiology; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D013737:Testis / Q000166:cytology / Q000196:embryology / Q000502:physiology