title: PIWI proteins are dispensable for mouse somatic development and reprogramming of fibroblasts into pluripotent stem cells.
abstract: PIWI proteins play essential and conserved roles in germline development, including germline stem cell maintenance and meiosis. Because germline regulators such as OCT4, NANOG, and SOX2 are known to be potent factors that reprogram differentiated somatic cells into induced pluripotent stem cells (iPSCs), we investigated whether the PIWI protein family is involved in iPSC production. We find that all three mouse Piwi genes, Miwi, Mili, and Miwi2, are expressed in embryonic stem cells (ESCs) at higher levels than in fibroblasts, with Mili being the highest. However, mice lacking all three Piwi genes are viable and female fertile, and are only male sterile. Furthermore, embryonic fibroblasts derived from Miwi/Mili/Miwi2 triple knockout embryos can be efficiently reprogrammed into iPS cells. These iPS cells expressed pluripotency markers and were capable of differentiating into all three germ layers in teratoma assays. Genome-wide expression profiling reveals that the triple knockout iPS cells are very similar to littermate control iPS cells. These results indicate that PIWI proteins are dispensable for direct reprogramming of mouse fibroblasts.
authors.affiliation: Yale Stem Cell Center and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Ee-Chun
authors.initials: EC
authors.lastname: Cheng
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors.forename: Dongwan
authors.initials: D
authors.lastname: Kang
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Yale Stem Cell Center and Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Haifan
authors.initials: H
authors.lastname: Lin
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D065150:Cellular Reprogramming / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D055786:Gene Knockout Techniques; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D060565:Argonaute Proteins; C546575:PIWIL4 protein, mouse; C448522:Piwil1 protein, mouse; C448521:Piwil2 protein, mouse