ABSTRACT
Although pluripotent stem cells can generate various types of differentiated cells, it is unclear why lineage-committed stem/progenitor cells derived from pluripotent stem cells are decelerated and why the differentiation-resistant propensity of embryonic stem cell (ESC)/induced pluripotent stem cell (iPSC)-derived cells is predominant compared with the in vivo equivalents derived from embryonic/adult tissues. In this study, we demonstrated that iPSCs reprogrammed and maintained with three chemical inhibitors of the fibroblast growth factor 4-mitogen-activated protein kinase cascade and GSK3ß (3i) could be differentiated into all three germ layers more efficiently than the iPSCs reprogrammed without the 3i chemicals, even though they were maintained with 3i chemicals once they were reprogrammed. Although the iPSCs reprogrammed with 3i had increased numbers of Zscan4-positive cells, the Zscan4-positive cells among iPSCs that were reprogrammed without 3i did not have an accelerated differentiation ability. These observations suggest that 3i exposure during the reprogramming period determines the accelerated differentiation/maturation potentials of iPSCs that are stably maintained at the distinct state.
Subject(s)
Biomarkers/metabolism , Cell Differentiation/physiology , Cellular Reprogramming/physiology , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/physiology , Animals , Cells, Cultured , Embryonic Stem Cells/metabolism , Embryonic Stem Cells/physiology , Fibroblast Growth Factor 4/metabolism , Germ Layers/metabolism , Germ Layers/physiology , Glycogen Synthase Kinase 3 beta/metabolism , MiceSubject(s)
Antipsychotic Agents/therapeutic use , Dopamine Antagonists/therapeutic use , Piperazines/therapeutic use , Piperidines/therapeutic use , Schizophrenia/drug therapy , Serotonin Antagonists/therapeutic use , Adult , Delusions/drug therapy , Hallucinations/drug therapy , Humans , Male , Treatment OutcomeSubject(s)
Capgras Syndrome/drug therapy , Catatonia/drug therapy , Hypothyroidism/drug therapy , Schizophrenia, Paranoid/drug therapy , Thyroxine/therapeutic use , Adult , Capgras Syndrome/complications , Capgras Syndrome/etiology , Catatonia/complications , Catatonia/etiology , Female , Humans , Hypothyroidism/complications , Hypothyroidism/diagnosis , Schizophrenia, Paranoid/complications , Schizophrenia, Paranoid/etiologyABSTRACT
Mixed-epithelial papillary cystadenoma of borderline malignancy of mullerian type (MEBMM) is composed of a mixture of mullerian epithelial types, such as mucinous, serous, endometrioid, and squamous. Four cases of MEBMM with squamous overgrowth (MEBMMSO) were reviewed. The patients' median age was 56 years, and all cases were unilateral. The clinical stages were Ia (two cases), Ic (one case), and IV based on the presence of tumor cells in pleural fluid (one case). No recurrence was seen in three of the cases. In one of those three cases, there was no recurrence after undergoing surgery only; in the other two of those three cases, there was no recurrence after undergoing surgery and receiving postoperative chemotherapy. In the single case that was at stage IV at initial presentation, a recurrent MEBMMSO nodule was found at a second look 17 months after the initial surgery. In terms of gross findings, all of the tumors were cystic with intracystic papillary fronds. In addition, old endometriotic lesions lined the cysts. The tumors were mainly composed of a proliferation of squamous-type epithelium, with minor foci containing a mixture of other mullerian-type epithelia, especially mucinous. Intraepithelial infiltration by neutrophilic leukocytes was prominent. The differential diagnosis of MEBMMSO includes proliferating Brenner tumors.
