Enhanced glycolysis is a main feature of pluripotent stem cells (PSCs) and is proposed to be important for the maintenance and induction of pluripotency. The molecular mechanism underlying enhanced glycolysis in PSCs is not clear. Using Dgcr8 À/À mouse embryonic stem cells (ESCs) that lack mature miRNAs, we found that miR-290 cluster of miRNAs stimulates glycolysis by upregulating glycolytic enzymes Pkm2 and Ldha, which are also essential for the induction of pluripotency during reprogramming. Mechanistically, we identified Mbd2, a reader for methylated CpGs, as the target of miR-290 cluster that represses glycolysis and reprogramming. Furthermore, we discovered Myc as a key target of Mbd2 that controls metabolic switch in ESCs. Importantly, we demonstrated that miR-371 cluster, a human homolog of miR-290 cluster, stimulates glycolysis to promote the reprogramming of human fibroblasts. Hence, we identified a previously unappreciated mechanism by which miR-290/371 miRNAs orchestrate epigenetic, transcriptional and metabolic networks to promote pluripotency in PSCs and during reprogramming.

The molecular mechanism controlling the dismantling of naive pluripotency is poorly understood. Here we show that microRNAs (miRNAs) have important roles during naive to primed pluripotency transition. Dgcr8−/− embryonic stem cells (ESCs) failed to completely silence the naive pluripotency program, as well as to establish the primed pluripotency program during differentiation. miRNA profiling revealed that expression levels of a large number of miRNAs changed dynamically and rapidly during naive to primed pluripotency transition. Furthermore, a miRNA screen identified numerous miRNAs promoting naive to primed pluripotency transition. Unexpectedly, multiple miRNAs from miR-290 and miR-302 clusters, previously shown as pluripotency-promoting miRNAs, demonstrated the strongest effects in silencing naive pluripotency. Knockout of both miR-290 and miR-302 clusters but not either alone blocked the silencing of naive pluripotency program. Mechanistically, the miR-290/302 family of miRNAs may facilitate the exit of naive pluripotency in part by promoting the activity of MEK pathway and through directly repressing Akt1. Our study reveals miRNAs as an important class of regulators potentiating ESCs to transition from naive to primed pluripotency, and uncovers context-dependent functions of the miR-290/302 family of miRNAs at different developmental stages.

Purpose An automatic evaluation technology based on artificial intelligence and three‐dimensional ultrasonography (3D US) is proposed for hip US inspection plane selection. This study aimed to evaluate the consistency of the α angle as measured using 3D US to select the section plane and two‐dimensional ultrasonography (2D US) to manually select the Graf image, as well as to explore the feasibility of diagnosing developmental dysplasia of the hip (DDH) using 3D US and reconstruction technology. Methods A total of 216 infant hips were included and assessed by doctors using 3D US layer‐by‐layer. The researchers used a computer to identify the coronal images that met the Graf standard and then compared the αX values obtained with the αG values measured artificially by 2D US. Results Compared with 2D US, 3D US more clearly showed the relative positions of the ilium, ischia, and pubis. The measured α value of the optimal section obtained by 3D US showed good agreement with the measured α value of the standard Graf section. Conclusion The artificial intelligence and 3D US‐based automatic evaluation technology for section selection and inspection for DDH showed good agreement with the Graf method based on standard sections.