Rapid loss of Oct-4 and pluripotency in cultured rodent blastocysts and derivative cell lines
Details
Publication Year 2003-01,Volume 68,Issue #1,Page 222-229
Journal Title
BIOLOGY OF REPRODUCTION
Publication Type
Journal Article
Abstract
The POU transcription factor Oct-4 is essential for the pluripotent character of the mouse inner cell mass (ICM) and derivative embryonic stem (ES) cells. We analyzed the expression of Oct-4 during culture and establishment of cell lines from mouse and rat preimplantation embryos. Oct-4 was rapidly lost in primary outgrowths of the majority of cultured embryos prior to any evidence of morphological differentiation. Oct-4 persisted in only a minority of strain 129 cultures, which can go on to give ES cells. We used transgenic rats in which the dual reporter/ selection marker beta-geo is under control of Oct-4 regulatory elements to investigate the effect of direct selection for Oct-4 expressing cells. Ablation of all cells occurred, consistent with complete downregulation of Oct-4. Without selection, in contrast, continuous cultures of morphologically undifferentiated cells could be derived readily from rat blastocysts and lCMs. However, these cells did not express significant Oct-4 and, although capable of differentiating into extraembryonic cell types, appeared incapable of producing fetal germ layer derivatives. Downregulation of Oct-4 appears to be a limiting factor in attempts to derive pluripotent cell lines from preimplantation embryos.
Publisher
SOC STUDY REPRODUCTION
Keywords
EMBRYONIC STEM-CELLS; DIFFERENTIATION INHIBITING ACTIVITY; TRANSCRIPTION FACTOR; MOUSE EMBRYO; ES CELLS; MAMMALIAN EMBRYO; ESTABLISHMENT; RAT; EXPRESSION; GERM
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Creation Date: 2003-01-01 12:00:00
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