PRDM14 maintains pluripotency of embryonic stem cells through TET-mediated active DNA demethylation.

Pluripotency and self-renewal of mouse embryonic stem cells (ESCs) depend on a network of transcription factors maintained by exogenous leukaemia inhibitory factor (LIF). PR-domain containing transcriptional regulator 14 (PRDM14), is essential for maintenance of ESC self-renewal when the cells are cultured in serum plus LIF, but not in 2i medium plus LIF. Here, we show that pluripotency of ESCs is maintained by enforced expression of PRDM14 at a high level, as observed in ESCs in 2i plus LIF and developing primordial germ cells in the absence of LIF. Constitutive expression of PRDM14 represses de novo DNA methylation in pluripotency-associated genes, resulting in the maintenance of gene expression after withdrawal of LIF, while also repressing the upregulation of differentiation markers. Further, knockdown of Tet1/Tet2 and administration of base excision repair (BER) pathway inhibitors impairs the PRDM14-induced resistance of ESCs to differentiation. We conclude that, in the absence of LIF, PRDM14 governs the retention of pluripotency-associated genes through the regulation of TET functions in the BER-mediated active demethylation pathway, while acting to exert TET-independent transcriptional repressive activity of several differentiation markers.

Comprehensive Health-Related Quality of Life is Influenced by Nocturia and Sleep Disturbance: Investigation Based on the SF-8.

We investigated the influence of nocturia and sleep disturbance on health-related quality of life(HRQOL) using the Medical Outcomes Study 8-item Short Form Health Survey (SF-8) in patients with nocturia. We also assessed the effect of therapeutic intervention by means of an anticholinergic agent on the results of the SF-8. One hundred and eighty-four patients who voided at least once per night were surveyed using the SF-8, Overactive Bladder Symptom Score (OABSS), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS). These parameters were also evaluated before and after 12 weeks of imidafenacin treatment in 51 patients with OAB accompanied by nocturia. The SF-8 physical component summary score (PCS) showed a significant decrease as nighttime voiding frequency increased. The mental health component summary score was 47.1 and 47.6 (which were lower than the standard value of 50) in the group with a nighttime frequency of once and ≥3/night, respectively. The SF-8 PCS and 6 subscales were negatively associated with nighttime voiding frequency, while the PSQI global score was positively associated with it. Imidafenacin significantly improved the OABSS, PSQI, and ESS, as well as the SF-8 score. This is the first study using the SF-8 to show that nocturia and sleep disturbance have a major influence on comprehensive HRQOL and that the SF-8 can be used to monitor HRQOL in OAB patients receiving treatment for nocturia.

PRDM14 Drives OCT3/4 Recruitment via Active Demethylation in the Transition from Primed to Naive Pluripotency.

Primordial germ cells (PGCs) are specified from epiblast cells in mice. Genes associated with naive pluripotency are repressed in the transition from inner cell mass to epiblast cells, followed by upregulation after PGC specification. However, the molecular mechanisms underlying the reactivation of pluripotency genes are poorly characterized. Here, we exploited the in vitro differentiation of epiblast-like cells (EpiLCs) from embryonic stem cells (ESCs) to elucidate the molecular and epigenetic functions of PR domain-containing 14 (PRDM14). We found that Prdm14 overexpression in EpiLCs induced their conversion to ESC-like cells even in the absence of leukemia inhibitory factor in adherent culture. This was impaired by the loss of Kruppel-like factor 2 and ten-eleven translocation (TET) proteins. Furthermore, PRDM14 recruited OCT3/4 to the enhancer regions of naive pluripotency genes via TET-base excision repair-mediated demethylation. Our results provide evidence that PRDM14 establishes a transcriptional network for naive pluripotency via active DNA demethylation.

[Paraurethral leiomyoma in women].

We experienced a case of paraurethral leiomyoma in a 36-year-old woman. She had been complaining of dysuria. She had noticed the presence of a mass in anterior vagina. That mass was about 3 x 3 cm, floating moderately firm with a smooth face sited in a paraurethral region. Magnetic resonance imaging showed medium-signal intensity on T1-weighted images and a homogeneous low signal on T2-weighted images. We diagnosed it as a paraurethral leiomyoma and enucleated it by surgery. At histological examination the tumor resulted in being a leiomyoma. The diagnosis and the treatment of female paraurethral leiomyoma are discussed.