// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Hyung Kwon Byeon1, Hwi Jung Na1, Yeon Ju Yang1, Sooah Ko1, Sun Och Yoon2, Minhee Ku3, 4, Jaemoon Yang3, 5, Jae Wook Kim6, Myung Jin Ban6, Ji-Hoon Kim7, Da Hee Kim1, Jung Min Kim1, Eun Chang Choi1, Chang-Hoon Kim1, 8, Joo-Heon Yoon1, 8, 9, Yoon Woo Koh1, 8 1Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea 2Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 3Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea 4Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea 5YUHS-KRIBB Medical Convergence Research Institute, Seoul, Republic of Korea 6Department of Otorhinolaryngology, Soonchunhyang University College of Medicine, Republic of Korea 7Department of Otorhinolaryngology-Head and Neck Surgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea 8The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea 9Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Yoon Woo Koh, email: ywkohent@yuhs.ac Keywords: thyroid cancer, molecular targeted therapy, drug resistance, BRAF mutation, epithelial-mesenchymal transition Received: September 23, 2016 Accepted: November 12, 2016 Published: November 21, 2016

During mouse gametogenesis, germ cells derived from the same progenitor are connected via intercellular bridges forming germline cysts, within which asymmetrical or symmetrical cell fate occurs in female and male germ cells, respectively. Here, we have identified branched cyst structures in mice, and investigated their formation and function in oocyte determination. In fetal female cysts, 16.8% of the germ cells are connected by three or four bridges, namely branching germ cells. These germ cells are preferentially protected from cell death and cyst fragmentation and accumulate cytoplasm and organelles from sister germ cells to become primary oocytes. Changes in cyst structure and differential cell volumes among cyst germ cells suggest that cytoplasmic transport in germline cysts is conducted in a directional manner, in which cellular content is first transported locally between peripheral germ cells and further enriched in branching germ cells, a process causing selective germ cell loss in cysts. Cyst fragmentation occurs extensively in female cysts, but not in male cysts. Male cysts in fetal and adult testes have branched cyst structures, without differential cell fates between germ cells. During fetal cyst formation, E-cadherin (E-cad) junctions between germ cells position intercellular bridges to form branched cysts. Disrupted junction formation in E-cad-depleted cysts led to an altered ratio in branched cysts. Germ cell-specific E-cad knockout resulted in reductions in primary oocyte number and oocyte size. These findings shed light on how oocyte fate is determined within mouse germline cysts.

In mammalian females, the transition from dormancy in primordial follicles to follicular development is critical for maintaining ovarian function and reproductive longevity. In mice, the quiescent primary oocyte of the primordial follicle contains a Balbiani body (B-body), an organelle aggregate comprised of a spherical structure of Golgi complexes. Here we show that the structure of the B-body is maintained by microtubules and actin. The B-body stores mRNA-capping enzyme and 597 mRNAs associated with mRNA-decapping enzyme 1 A (DCP1A). Gene ontology analysis results indicate that proteins encoded by these mRNAs function in enzyme binding, cellular component organization and packing of telomere ends. Pharmacological depolymerization of microtubules or actin led to B-body disassociation and nascent protein synthesis around the dissociated B-bodies within three hours. An increased number of activated developing follicles were observed in ovaries with prolonged culture and the in vivo mouse model. Our results indicate that the mouse B-body is involved in the activation of dormant primordial follicles likely via translation of the B-body-associated RNAs in primary oocytes.

Https://doi.org/10.18632/oncotarget.28074 Nicholas Cho, Sooah Ko, Monica Shokeen

The interaction between CD47 expressed on cancer cells and signal regulatory protein-α located on macrophages blocks the phagocytosis of tumor cells by macrophages. Our data reveal that human endometrial cancer cells (hECCs) upregulate the CD47 level on their surface and that there is a high density of tumor-associated macrophages within the microenvironment of human endometrial cancer. In vitro functional assay shows that an anti-CD47 monoclonal antibody (mAb) promotes the phagocytosis of hECCs by macrophages. Systemic and in situ treatments with an anti-CD47 mAb effectively reduce tumor burden in vivo in a genetically engineered mouse model of endometrial cancer. Thus, this study provides preclinical evidence that CD47 blockade using an anti-CD47 mAb to augment macrophage phagocytosis is a potential therapeutic strategy for endometrial cancer.