Project description:Human preimplantation development involves extensive remodeling of RNA expression and splicing. However, its transcriptome has been compiled using short-read sequencing data, which fails to capture most full-length mRNAs. Here, we generate an isoform-resolved transcriptome of early human development by performing long- and short-read RNA sequencing on 73 embryos spanning the zygote to blastocyst stages. We identify 110,212 unannotated isoforms transcribed from known genes, including highly conserved protein-coding loci and key developmental regulators. We further identify 17,964 isoforms from 5,239 unannotated genes, which are largely non-coding, primate-specific, and highly associated with transposable elements. These isoforms are widely supported by the integration of published multi-omics datasets, including single-cell 8CLC and blastoid studies. Alternative splicing and gene co-expression network analyses further reveal that embryonic genome activation is associated with splicing disruption and transient upregulation of gene modules. Together, these findings show that the human embryo transcriptome is far more complex than currently known, and will act as a valuable resource to empower future studies exploring development.
Project description:Human preimplantation development is a complex process involving extensive remodeling of gene expression. However, the preimplantation embryo transcriptome has only been annotated using short-read sequencing, which fails to capture full-length mRNAs and associated isoform diversity. We present a novel human embryo transcriptome using integrated long- and short-read RNA sequencing data. Our analysis reveals a total of 110,212 novel isoforms transcribed from known genes containing either a novel combination of known splice sites or at least one novel splice site, and 17,964 isoforms transcribed from completely novel genes located either in antisense direction of known genes or in intergenic space.
Project description:Human preimplantation development is a complex process involving extensive remodeling of gene expression. However, the preimplantation embryo transcriptome has only been annotated using short-read sequencing, which fails to capture full-length mRNAs and associated isoform diversity. We present a novel human embryo transcriptome using integrated long- and short-read RNA sequencing data. Our analysis reveals a total of 110,212 novel isoforms transcribed from known genes containing either a novel combination of known splice sites or at least one novel splice site, and 17,964 isoforms transcribed from completely novel genes located either in antisense direction of known genes or in intergenic space.
