Systems Genetics Implicates Cytoskeletal Genes in Oocyte Control of Cloned Embryo Quality. Cheng Y et al. Cloning by somatic cell nuclear transfer is an important technology, but remains limited due to poor rates of success. Identifying genes supporting clone development would enhance our understanding of basic embryology, improve applications of the technology, support greater understanding of establishing pluripotent stem cells, and provide new insight into clinically important determinants of oocyte quality. For the first time, a systems genetics approach was taken to discover genes contributing to the ability of an oocyte to support early cloned embryo development. This identified a primary locus on mouse chromosome 17 and potential loci on chromosomes 1 and 4. A combination of oocyte transcriptome profiling data, expression correlation analysis, functional and network analyses yielded a short list of likely candidate genes in two categories. The major category-including two genes with the strongest genetic associations with the traits (Epb4.1l3 and Dlgap1)-encodes proteins associated with the subcortical cytoskeleton and other cytoskeletal elements such as the spindle. The second category encodes chromatin and transcription regulators (Runx1t1, Smchd1, and Chd7). Smchd1 promotes X chromosome inactivation, whereas Chd7 regulates expression of pluripotency genes. Runx1t1 has not been associated with these processes, but acts as a transcriptional repressor. The finding that cytoskeleton-associated proteins may be key determinants of early clone development highlights potential roles for cytoplasmic components of the oocyte in supporting nuclear reprogramming. The transcriptional regulators identified may contribute to the overall process as downstream effectors.
Expression regulated by
Oocyte, Cumulus, Granulosa
Differential expression of poliovirus receptor, regulator of G-protein signaling 11 and erythrocyte protein band 4.1-like 3 in human granulosa cells during follicular growth and maturation. Barzilay E 2014 et al.
Abstract Poliovirus receptor (PVR), regulator of G-protein signaling-11 (RGS11), and erythrocyte protein band-4.1-like 3 (EPB41L3) have been proposed to function in follicular maturation in mouse models. We have examined their expression in human mural (mGCs) and cumulus granulosa cells (CCs). Expression of PVR and RGS11 in mGCs decreased in medium-sized follicles compared to small follicles of IVM cycles and increased again in large follicles. Luteinization caused decreased expression of both PVR and RGS11. In vitro incubation of mGCs with progesterone-rich conditioned media decreased expression of RGS11 without affecting PVR levels. Inhibition of progesterone signaling enhanced expression of both RGS11 and PVR. Expression in CCs was examined by means of global transcriptome sequencing analysis RGS11 and EPB41L3 increased in CCs during follicular maturation while PVR levels did not change. In conclusion, during human follicular maturation there are significant changes in expression of PVR, RGS11 and EPB41L3, possibly regulated by progesterone.
Expression Patterns of Poliovirus Receptor, Erythrocyte Protein Band 4.1-Like 3, Regulator of G-Protein Signaling 11 and Oxytocin Receptor in Mouse Ovarian Cells During Follicle Growth and Early Luteinization In Vitro and In Vivo. Segers I et al. Poliovirus receptor (Pvr), erythrocyte protein band 4.1-like 3 (Epb4.1l3), regulator of G-protein signaling 11 (Rgs11), and oxytocin receptor (Oxtr) expression were quantified in in vitro and in vivo grown mouse follicles. The expression of all genes was increased during antral growth in in vitro grown cumulus cells, while only Rgs11 and Oxtr were increased and Pvr and Epb4.1l3 were decreased in in vivo grown cumulus cells. In vivo mural granulosa cells showed the highest expression of Pvr, Rgs11, and Oxtr. The in vitro granulosa+theca compartment responded to hCG during early luteinization by either an up regulation (Pvr, Oxtr) or down regulation (Epb41l3, Rgs11). Oocytes expressed Epb4.1l3, not Rgs11, and Pvr only in in vitro grown oocytes. Translation into protein was confirmed for Epb4.1l3 in in vitro grown follicles and in vivo grown cumulus oocyte complexes. Protein 4.1B was present during antral growth in cumulus, granulosa cells and oocytes. Hypothetical functions of Epb4.1l3 and Pvr involve cell adhesion regulation and Rgs11 could be cAMP production in the follicle. Oxtr is known to be important during and after the ovulatory stimulus, but as in bovine, was also regulated during folliculogenesis. High expression of Pvr and Epb4.1l3 with culture duration in cumulus cells might mark the inappropriate differentiation into a mural granulosa-like cell type and function as negative follicle development marker. Rgs11 and Oxtr are both in vivo and in vitro up regulated in cumulus cells during antral follicle growth and might be considered positive markers for follicle development.