Project description:The cellular evolutions and molecular programs underlying the arteriovenous fate settling of embryonic vascular endothelial cells (ECs) are critical for understanding arteriogenesis and inspiring new approaches for regenerative biology. Using different strategies of single-cell RNA sequencing, we constructed the transcriptional landscape of early arteriovenous EC development in both mouse and human embryos, demonstrating the evolutionary conservation of principal vascular EC types and providing a series of conserved arteriovenous genes. We showed an unexpected diversity of arteriovenous characteristics in morphologically alike vascular plexus and further uncovered two transcriptomically distinct arterial EC types, whereas most of heterologous ligand-receptor pairs were shared by different arterial vasculatures. By computational predicting and further genetic lineage tracing, we revealed the widespread venous arterialization in the mid-gestational mouse embryo proper. Interestingly, we demonstrated at transcriptomic level that Notch1 was dispensable for venous arterialization but required subsequently for the arterial feature strengthening in the arterial plexus ECs. Altogether, our findings unprecedentedly detail the comprehensive single-cell mapping of early embryonic vascular ECs in vivo, decipher an asymmetric arteriovenous characteristics different than that in adults, and reveal an extensive venous-to-arterial fate conversion in the vascular plexus.
Project description:In this project, we profiled the dynamics of proteome during Arabidopsis early embryogenesis using nanoproteomics. In addition, we identified some proteins which may be important during this process. Combining with RNA-seq, we unveiled the relationship between RNA and proteins during Arabidopsis early embryogenesis.
Project description:Early vertebrate embryogenesis is characterized by extensive post-transcriptional regulation during the maternal-to-zygotic transition. The N6-methyladenosine (m6A) modifications on mRNA has been shown to affect both translation and stability of transcripts. Here we investigate the m6A topology during early vertebrate embryogenesis and its association with RNA stability, translation efficiency and effect on miR-430 degradation kinetics. Notably, we find a strong association of m6A with cytoplasmic polyadenylation and translational efficiency prior to zygotic genome activation. Genes required for zygotic genome activation such as nanog and pou5f3 display dynamic m6A levels. After zygotic genome activation m6A is associated with improved stability and dampens the effect of miR-430 mediated degradation. Through sequence analyses we identified enrichment of motifs for RNA binding proteins involved in translational regulation and RNA degradation. We propose a role for m6A in multiple mRNA regulatory mechanisms, for the first time in an in vivo system and improve our understanding of the combinatorial code behind the complex post transcriptional regulation of reprogramming during early vertebrate development.
Project description:Stem cells are regulated by transcriptional networks controlling pluripotency and differentiation. How basic cellular processes like splicing or protein synthesis regulate stem cell function is less well understood. Here, we show that the RNA binding protein HTATSF1 controls protein synthesis by controlling several independent RNA processing steps during ribosome biogenesis. In a complex with ribosomal RNA transcription and processing factors, HTATSF1 regulates ribosomal RNA abundance. By binding to the U2snRNP complex, HTATSF1 also controls intron removal specifically in ribosomal protein transcripts. HTATSF1-mediated control of protein synthesis is essential for the transition from the naïve pre-implantation epiblast to the primed post-implantation epiblast, a stage of low protein synthesis levels, and during further differentiation towards neuroectoderm. Our results identify coordinated regulation of ribosomal RNA and protein biosynthesis by HTATSF1 as an essential mechanism to mediate protein synthesis control during early stages of mammalian embryogenesis.
Project description:Stem cells are regulated by transcriptional networks controlling pluripotency and differentiation. How basic cellular processes like splicing or protein synthesis regulate stem cell function is less well understood. Here, we show that the RNA binding protein HTATSF1 controls protein synthesis by controlling several independent RNA processing steps during ribosome biogenesis. In a complex with ribosomal RNA transcription and processing factors, HTATSF1 regulates ribosomal RNA abundance. By binding to the U2snRNP complex, HTATSF1 also controls intron removal specifically in ribosomal protein transcripts. HTATSF1-mediated control of protein synthesis is essential for the transition from the naïve pre-implantation epiblast to the primed post-implantation epiblast, a stage of low protein synthesis levels, and during further differentiation towards neuroectoderm. Our results identify coordinated regulation of ribosomal RNA and protein biosynthesis by HTATSF1 as an essential mechanism to mediate protein synthesis control during early stages of mammalian embryogenesis.
Project description:Stem cells are regulated by transcriptional networks controlling pluripotency and differentiation. How basic cellular processes like splicing or protein synthesis regulate stem cell function is less well understood. Here, we show that the RNA binding protein HTATSF1 controls protein synthesis by controlling several independent RNA processing steps during ribosome biogenesis. In a complex with ribosomal RNA transcription and processing factors, HTATSF1 regulates ribosomal RNA abundance. By binding to the U2snRNP complex, HTATSF1 also controls intron removal specifically in ribosomal protein transcripts. HTATSF1-mediated control of protein synthesis is essential for the transition from the naïve pre-implantation epiblast to the primed post-implantation epiblast, a stage of low protein synthesis levels, and during further differentiation towards neuroectoderm. Our results identify coordinated regulation of ribosomal RNA and protein biosynthesis by HTATSF1 as an essential mechanism to mediate protein synthesis control during early stages of mammalian embryogenesis.
Project description:To determine the transcriptional effects of lack of Tet proteins during early embryogenesis, we performed single-embryo RNA-sequencing of control and TKO embryos (E6.75; 4 embryos from each group). Genome-wide analyses showed that Tet deficiency promotes the expression of mesoderm-related genes during early embryogenesis in vivo.