MPP8 Governs the Activity of the LIF/STAT3 Pathway and Plays a Crucial Role in the Differentiation of Mouse Embryonic Stem Cells.

Mouse embryonic stem cells (mESCs) possess the remarkable characteristics of unlimited self-renewal and pluripotency, which render them highly valuable for both fundamental research and clinical applications. A comprehensive understanding of the molecular mechanisms underlying mESC function is of the utmost importance. The Human Silence Hub (HUSH) complex, comprising FAM208A, MPP8, and periphilin, constitutes an epigenetic silencing complex involved in suppressing retroviruses and transposons during early embryonic development. However, its precise role in regulating mESC pluripotency and differentiation remains elusive. In this study, we generated homogenous miniIAA7-tagged Mpp8 mouse ES cell lines. Upon induction of MPP8 protein degradation, we observed the impaired proliferation and reduced colony formation ability of mESCs. Furthermore, this study unveils the involvement of MPP8 in regulating the activity of the LIF/STAT3 signaling pathway and Nanog expression in mESCs. Finally, we provide compelling evidence that degradation of the MPP8 protein impairs the differentiation of mESC.

A One-step strategy to target essential factors with auxin-inducible degron system in mouse embryonic stem cells.

The self-renewal and pluripotency of embryonic stem cells (ESCs) are conferred by networks including transcription factors and histone modifiers. The Auxin-inducible degron (AID) system can rapidly and reversibly degrade its target proteins and is becoming a powerful tool to explore novel function of key pluripotent and histone modifier genes in ESCs. However, the low biallelic tagging efficiency and a basal degradation level of the current AID systems deem it unsuitable to target key pluripotent genes with tightly controlled expression levels. Here, we develop a one-step strategy to successfully target and repress the endogenous pluripotent genes in mouse ESCs and replace their expression with AID fused transgenes. Therefore, this work provides an efficient way for employing the AID system to uncover novel function of essential pluripotent and chromatin modifier genes in ESCs.

[Efficacy analysis of endoscopic submucosal dissection for the early cancer and precancerous lesions in the remnant stomach].

OBJECTIVE: To determine the feasibility and efficacy of endoscopic submucosal dissection(ESD) in treating early gastric cancer(EGC) and precancerous lesions in the remnant stomach of patients after gastrectomy. METHODS: Clinical data of 36 patients with EGC and precancerous lesions in remnant stomach undergoing ESD in Endoscopy Center of Zhongshan Hospital from January 2008 to December 2013 were retrospectively analyzed. Operative, postoperative conditions and long-term follow-up of these patients were evaluated. RESULTS: Both the success rate and the complete resection rate were 100%. The average maximum diameter of the tumor was 1.5(range 0.6-4.5) cm. During the ESD process, two bleeding cases were treated successfully by endoscopic hemostasis. The average operation time was 40(10-80) min. The delayed hemorrhage developed in 2 cases within 1-3 days after operation, and were also treated successfully by endoscopic hemostasis. There was no perforation or delayed perforation. No emergency surgery was required for the complication. Twelve cases were diagnosed as mild-moderate dysplasia, 7 cases as high grade intraepithelial neoplasia, 16 cases as hyperplastic polyps, and 1 case as signet ring cell carcinoma with T1 stage, who underwent operation for resecting gastric stump and lymph node dissection 7 days after ESD without subsequent follow-up. The curative resection rate was 92.7%(35/36). The median follow-up of the remaining 35 patients was 36(6-78) months without discomfort and recurrence under gastroscopy. CONCLUSION: ESD is safe and effective for EGC and precancerous lesions in the remnant stomach.