Translatome and transcriptome co-profiling reveals a role of TPRXs in human zygotic genome activation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE197265 | GEO | 2022/10/08
REPOSITORIES: GEO
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Project description:Oocyte-to-embryo transition plays a critical role in oocyte maturation and embryogenesis. It is a highly regulated process in part due to a transcription silenced period followed by zygotic genome activation. How transcriptome, translatome, and proteome interplay in this critical developmental window remains poorly understood. Utilizing a highly sensitive mass spectrometry, we obtained a high-quality proteome landscape spanning 10 stages, from the mouse full-grown oocyte (FGO) to blastocyst, using 100 oocytes/embryos at each stage. By integrative analysis with corresponding transcriptome and translatome, we found transcription and translation levels can not reflect protein abundance in most cases. From FGO to 4-cell embryos, proteomes are predominated by FGO-produced proteins, while the transcriptome and translatome are much more dynamic. FGO inherited proteins frequently persist after the corresponding transcripts are already downregulated or decayed. Improved concordance between protein and RNA is observed for genes starting translation only upon meiotic resumption (OET upregulated) or transcribed only in embryos, although the detected protein dynamics often lag behind transcription and translation. Concordance between protein and transcription/tranlation is associated with protein half-lives. Finally, a kinetic model well predicts protein dynamics when incorporating both the initial protein abundance in FGO and translation kinetics across developmental stages. In sum, our study reveals multilayer control of gene expression during oocyte maturation and embryogenesis.
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Project description:The remodelling of the epigenome and transcriptome of the fertilised oocyte to establish totipotency in the zygote and developing embryo is one of the most critical processes in mammalian embryogenesis. Zygotic or embryonic genome activation (ZGA, EGA) in the 2-cell embryo in mouse, and the 8-cell embryo in humans, constitutes the first major wave of transcription. Failure to initiate ZGA leads to developmental defects, and contributes to the high attrition rates of human pre-implantation embryos. Due to limitations in cell numbers and experimental tractability, the mechanisms that regulate human embryonic genome activation in the totipotent embryo remain poorly understood. Here we report the discovery of human 8-cell like cells (8CLCs) specifically among naïve embryonic stem cells, but not primed pluripotent cells. 8CLCs express ZGA marker genes, such as ZSCAN4, LEUTX and DUXA, and their transcriptome closely resembles that of the 8-cell human embryo. 8-cell like cells reactivate 8-cell stage specific transposable elements such as HERVL and MLT2A1, and are characterized by upregulation of the methylation regulator DPPA3. 8CLCs show reduced SOX2 protein levels and can be identified based on expression of the novel protein marker TPRX1 in vitro. Overexpression of the transcription factor DUX4 not only increases ZGA-like transcription, but also enhances TPRX1+ 8CLCs formation. The discovery of 8CLCs provides a unique opportunity to model and manipulate human ZGA-like transcriptional programs in vitro, and will provide critical functional insights into one of the earliest events in human embryogenesis in vivo.
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