title: Mouse embryonic stem cells form follicle-like ovarian structures but do not progress through meiosis.
abstract: Several recent studies have suggested that mouse embryonic stem cells (ESCs) can differentiate into female and male germ cells in vitro. The meiotic process in germ cell-like cells derived from ESCs has not been studied in detail, but it has been reported that synaptonemal complex protein-3 (SYCP3) is expressed in these cells. Here, we have carefully evaluated the meiotic process in germ cell-like cells derived from ESCs, using a panel of meiosis-specific markers that identify distinct meiotic signatures unique to meiotic prophase I development in vivo. We find that whereas SYCP3 is expressed in germ cell-like cells, other meiotic proteins, such as SYCP1, SYCP2, STAG3 (stromal antigen 3), REC8 (meiotic protein similar to the rad21 cohesins), and SMC1 (structural maintenance of chromosomes-1)-beta, are not expressed. The nuclear distribution of SYCP3 in the germ cell-like cells is highly abnormal and not associated with the chromosomes of these cells. Fluorescence in situ hybridization analysis shows that the SYCP3-positive germ cell-like cells do not contain synapsed homologous chromosomes but instead display a chromosomal organization normally found in somatic cells. The absence of expression of essential meiotic proteins and a normal meiotic chromosomal organization strongly suggests that the germ cell-like cells formed from ESCs fail to progress through meiosis.
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
authors.forename: Ivana
authors.initials: I
authors.lastname: Novak
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Lightfoot
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Annika
authors.initials: A
authors.lastname: Eriksson
authors.forename: Ensaf
authors.initials: E
authors.lastname: Mahdy
authors.forename: Christer
authors.initials: C
authors.lastname: Höög
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D006080:Ovarian Follicle / Q000166:cytology* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C490062:Sycp3 protein, mouse; D004958:Estradiol