Mouse embryonic stem cells form follicle-like ovarian structures but do not progress through meiosis.
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.
Novak
Ivana
I
Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Lightfoot
Daniel A
DA
Wang
Hong
H
Eriksson
Annika
A
Mahdy
Ensaf
E
Höög
Christer
C
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*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C490062:Sycp3 protein, mouse; D004958:Estradiol