Induced pluripotent stem (iPS) cells are reprogrammed from somatic cells through ectopic expression of stem cell-specific transcription factors, including Oct4, Nanog, Sox2, Lin28, Klf4, and c-Myc. Although iPS cells are similar to embryonic stem (ES) cells in their pluripotency, their inherited defects, such as insertion mutagenesis, employment of oncogenes, and low efficiency, associated with the reprogramming procedure have hindered their clinical application. A study has shown that valproic acid (VPA) treatment can significantly enhance the reprogramming efficiency and avoid the usage of oncogenes. To understand how VPA can enhance pluripotency, we stably transfected an Oct4 promoter driven luciferase reporter (Oct4-1.9k-Luc) into P19 embryonic carcinoma (EC) cells and C2C12 myoblasts and examined their response to VPA. We found that VPA could both activate Oct4 promoter and rescue its inhibition by retinoic acid (RA). In C2C12 myoblasts, VPA treatment also enhanced endogenous Oct4 expression but repressed that of MyoD. Furthermore, both RARalpha over-expression and mutation of a proximal hormone response element (HRE) blocked the activation effect of VPA on Oct4 promoter, implying that VPA may exert its activation effect through factors targeting this HRE. Taken together, these observations identify a molecular mechanism by which VPA directly regulate Oct4 expression to ensure the acquirement and maintenance of pluripotency.
This study investigated the relationship between dream lucidity, i.e., a dreamer’s insight to the ongoing dream, and attention by considering lucidity as a trait. We examined the ways in which lucidity correlates with the orienting, alerting, and conflict components of the attentional network. A total of 77 participants rated the lucidity of their dreams over 7 consecutive days with the LuCiD scale and then completed the attentional network task (ANT). A negative correlation between trait lucidity and the conflict score of the ANT was found for 49 participants whose responses were faster when an alerting signal was presented. This result suggested that, with a prerequisite that the presence of cues facilitates subsequent information processing, the greater a person’s trait lucidity, the more efficiently he or she is capable of resolving conflicts.
Induced pluripotent stem cells (iPS) are derived from somatic cells through ectopic expression of stem cell‐specific transcription factors, including Oct4, Nanog, Sox2, Lin28, Klf4 and c‐Myc. Although these iPS cells are similar to embryonic stem (ES) cells in their pluripotency, a few defects, such as insertion mutagenesis, employment of oncogenes, and low efficiency, associated with the procedure of creating them have hindered their clinical application. A study has shown that concomitant treatment with valproic acid (VPA) can significantly enhance the efficiency and avoid the usage of oncogenes. To elucidate the mechanisms of VPA enhanced pluripotency, we stably transfected a luciferase reporter (Oct4‐1.9k‐Luc) driven by the promoter of Oct4 into P19 embryonic carcinoma (EC) cells and C2C12 myoblasts to examine their response to VPA. By treating them with retinoic acid (RA) and VPA, we found that VPA could both activate Oct4 promoter and rescue its inhibition by retinoic acid. VPA treatment also enhanced endogeneous Oct4 expression but repressed that of MyoD in C2C12 myoblasts. These observations suggest that VPA enhances pluripotency by direct activating Oct4 transcription and repressing those of differentiation genes. Besides, our results imply that VPA may exert its effect through specific promoter‐targeting factors instead of through general effects on chromatin structure.
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