Homeostatic regulation of lipid droplet content in mammalian oocytes and embryos

Lipid droplets (LDs) consist of a core of neutral lipids such as triacylglycerols and cholesteryl esters covered by a phospholipid monolayer. Recent studies have shown that LDs not only store neutral lipids but are also associated with various physiological functions. LDs are found in most eukaryotic cells and vary in size and quantity. It has long been known that mammalian oocytes contain LDs. Porcine and bovine oocytes contain substantial amounts of LDs, which cause their cytoplasm to darken, whereas mouse and human oocytes are translucent due to their low LD content. A sufficient amount of LDs in mammalian oocytes has been thought to be associated with oocyte maturation and early embryonic development, but the necessity of LDs has been questioned because embryonic development proceeds normally even when LDs are removed. However, recent studies have revealed that LDs play a crucial role during implantation and that maintaining an appropriate amount of LDs is important for early embryonic development, even in mammalian species with low amounts of LDs in their oocytes. This suggests that a fine-tuned balance of LD content is essential for successful mammalian embryonic development. In this review, we discuss the physiological importance of LDs in mammalian oocytes and preimplantation embryos based on recent findings on LD biology.

Live imaging YAP signaling in vivo with fusion reporter mice

YAP protein is a critical regulator of mammalian embryonic development. By generating a near-infrared fusion YAP reporter mouse line, we have achieved high-resolution live imaging of YAP localization during mouse embryonic development. We have validated the reporter by demonstrating its predicted responses to blocking Lats kinase activity or blocking cell polarity. The YAP fusion reporter mice and imaging methods will open new opportunities for understanding dynamic YAP signaling in vivo in many different situations.

The evolutionary acquisition and mode of functions of promoter-associated non-coding RNAs (pancRNAs) for mammalian development

Increasing evidence has shown that many long non-coding RNAs (lncRNAs) are involved in gene regulation in a variety of ways such as transcriptional, post-transcriptional and epigenetic regulation. Promoter-associated non-coding RNAs (pancRNAs), which are categorized into the most abundant single-copy lncRNA biotype, play vital regulatory roles in finely tuning cellular specification at the epigenomic level. In short, pancRNAs can directly or indirectly regulate downstream genes to participate in the development of organisms in a cell-specific manner. In this review, we will introduce the evolutionarily acquired characteristics of pancRNAs as determined by comparative epigenomics and elaborate on the research progress on pancRNA-involving processes in mammalian embryonic development, including neural differentiation.

ZFP207 controls pluripotency by multiple post-transcriptional mechanisms

The pluripotent state is not solely governed by the action of the core transcription factors Oct4, Sox2, and Nanog, but also by a series of co-transcriptional and post-transcriptional events, including alternative splicing (AS) and the interaction of RNA-binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize the role of ZFP207 in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, ZFP207 does not transcriptionally regulate stem cell and neuronal-related genes but exerts its effects by control AS networks and acting as an RBP. Our study expands the role of ZFP207 to maintain ESC identity, and underscores ZFP207 functional versatility with key roles in neural fate commitment.

Features of DNA Repair in the Early Stages of Mammalian Embryonic Development

Cell repair machinery is responsible for protecting the genome from endogenous and exogenous effects that induce DNA damage. Mutations that occur in somatic cells lead to dysfunction in certain tissues or organs, while a violation of genomic integrity during the embryonic period often leads to death. A mammalian embryo’s ability to respond to damaged DNA and repair it, as well as its sensitivity to specific lesions, is still not well understood. In this review, we combine disparate data on repair processes in the early stages of preimplantation development in mammalian embryos.

Klf4 methylated by Prmt1 is required for lineage segregation of epiblast and primitive endoderm

The second cell fate decision in the early stage of mammalian embryonic development is pivotal; however, the underlying molecular mechanism is largely unexplored. Here, we report that Prmt1 acts as an important regulator in primitive endoderm (PrE) formation. First, an embryonic chimeric assay showed that Prmt1 inhibition induces the integration of mouse embryonic stem cells (ESCs) into the PrE. Second, Prmt1 inhibition promotes Gata6 expression in both mouse blastocysts and ESCs. Single-cell RNA sequencing and flow cytometry assays demonstrated that Prmt1 depletion in ESCs contributes to an emerging cluster, where PrE genes are upregulated significantly. Furthermore, the efficiency of extraembryonic endoderm stem cell induction increased in Prmt1-depleted ESCs. Finally, we showed that the pluripotency factor Klf4 methylated at Arg396 by Prmt1 is required for recruitment of the repressive mSin3a/HDAC complex to silence PrE genes. Therefore, we reveal a regulatory mechanism for cell fate decisions centered on Prmt1-mediated Klf4 methylation.

Early mammalian development: from basic research to the clinic

Preimplantation embryonic development lays the foundations for the future individual. Fertilization, cleavage, differentiation of the first embryonic cell lineages and implantation of the embryo into the maternal uterus are absolutely critical for proper embryogenesis. Solving unanswered questions as well as creating new ideas and theories constitute the main axis of the basic research, which is driven by the curiosity of scientists and their desire to explore the unknown. We researchers have been exploring the development of mammalian embryos for decades, searching for the answer to the most fundamental question in the whole area of biology: how a complex organism derives from a single totipotent cell, a zygote. Due to obvious ethical concerns, animals, such as mice and, currently more and more often, cattle, pigs and rabbits, have become useful models for studying human embryonic development. Unprecedented advancement in cell and molecular biology techniques witnessed in the last years allows us to deepen our understanding of mammalian embryonic development.