Reconstitution of the oocyte transcriptional network with transcription factors. Hamazaki N et al. (2020) During female germline development, oocytes become a highly specialized cell type and form a maternal cytoplasmic store of crucial factors. Oocyte growth is triggered at the transition from primordial to primary follicle and is accompanied by dynamic changes in gene expression1, but the gene regulatory network that controls oocyte growth remains unknown. Here we identify a set of transcription factors that are sufficient to trigger oocyte growth. By investigation of the changes in gene expression and functional screening using an in vitro mouse oocyte development system, we identified eight transcription factors, each of which was essential for the transition from primordial to primary follicle. Notably, enforced expression of these transcription factors swiftly converted pluripotent stem cells into oocyte-like cells that were competent for fertilization and subsequent cleavage. These transcription-factor-induced oocyte-like cells were formed without specification of primordial germ cells, epigenetic reprogramming or meiosis, and demonstrate that oocyte growth and lineage-specific de novo DNA methylation are separable from the preceding epigenetic reprogramming in primordial germ cells. This study identifies a core set of transcription factors for orchestrating oocyte growth, and provides an alternative source of ooplasm, which is a unique material for reproductive biology and medicine.//////////////////
NCBI Summary:
Cytoplasmic dyneins are large enzyme complexes with a molecular mass of about 1,200 kD. They contain two force-producing heads formed primarily from dynein heavy chains, and stalks linking the heads to a basal domain, which contains a varying number of accessory intermediate chains. The complex is involved in intracellular transport and motility. The protein described in this record is a light chain and exists as part of this complex but also physically interacts with and inhibits the activity of neuronal nitric oxide synthase. Binding of this protein destabilizes the neuronal nitric oxide synthase dimer, a conformation necessary for activity, and it may regulate numerous biologic processes through its effects on nitric oxide synthase activity. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]
General function
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Cellular localization
Cytoplasmic
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Ovarian function
Initiation of primordial follicle growth, Oogenesis, Oocyte maturation
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Expression regulated by
LH
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Ovarian localization
Oocyte, Granulosa
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Identification of oocyte-expressed genes abundant in fetal ovary Yao et al 2004 .
The bovine oocyte microarray was used to identify genes highly expressed in fetal ovary (an enriched source of oocytes) relative to adult spleen and liver tissues. The goal of this experiment was to validate utility of the cDNA microarray and to identify additional oocyte-expressed genes abundant in fetal ovary relative to somatic tissues. Microarray experiments with fetal ovary vs. spleen revealed 24 clones with >2-fold higher expression in fetal ovary (P < 0.05). Likewise, microarray experiments comparing fetal ovary and liver RNA revealed 98 clones with >2-fold higher expression in fetal ovary (P < 0.05). Overall, 11 clones were found to be in common between the lists of genes expressed at higher levels (>2-fold) in fetal ovary than in either spleen or liver. These 11 clones were retrieved from the original source plates and subjected to DNA sequencing. Sequence analysis revealed that these 11 clones represent 7 different genes. Two clones encode for JY-1, a known bovine oocyte-specific gene (Yao J, Huang R, Kobayashi Y, Bettegowda A, Coussens PM, Ireland JJ, and Smith GW. Identification and characterization of expression of JY-1: a novel oocyte specific gene in cattle. Biol Reprod 68: 112, 2003.). Eight of the remaining nine clones encode for five previously identified genes (ribosomal protein L7a, dynein light chain, Doc2 , calmodulin, leucine-rich protein). The final clone encodes for a completely novel transcript (Table 3). Since a heterogeneous tissue source including both oocytes and somatic cells (fetal ovary) was used as an enriched source of bovine oocytes for microarray analysis, expression of above-described genes in isolated bovine oocytes (from adult ovaries) was confirmed by real-time RT-PCR analysis (Fig. 3).
Changes in mouse granulosa cell gene expression during early luteinization. McRae RS et al. Changes in gene expression during granulosa cell luteinization have been measured using serial analysis of gene expression (SAGE). Immature normal mice were treated with pregnant mare serum gonadotropin (PMSG) or PMSG followed, 48 h later, by human chorionic gonadotropin (hCG). Granulosa cells were collected from preovulatory follicles after PMSG injection or PMSG/hCG injection and SAGE libraries generated from the isolated mRNA. The combined libraries contained 105,224 tags representing 40,248 unique transcripts. Overall, 715 transcripts showed a significant difference in abundance between the two libraries of which 216 were significantly down-regulated by hCG and 499 were significantly up-regulated. Among transcripts differentially regulated, there were clear and expected changes in genes involved in steroidogenesis as well as clusters of genes involved in modeling of the extracellular matrix, regulation of the cytoskeleton and intra and intercellular signaling. The SAGE libraries described here provide a base for functional investigation of the regulation of granulosa cell luteinization.