Isoform-resolved transcriptome of the human preimplantation embryo

Denis Torre, Nancy J. Francoeur, Yael Kalma, Ilana Gross Carmel, Betsaida S. Melo, Gintaras Deikus, Kimaada Allette, Ron Flohr, Maya Fridrikh, Konstantinos Vlachos, Kent Madrid, Hardik Shah, Ying Chih Wang, Shwetha H. Sridhar, Melissa L. Smith, Efrat Eliyahu, Foad Azem, Hadar Amir, Yoav Mayshar, Ivan MarazziErnesto Guccione, Eric Schadt, Dalit Ben-Yosef*, Robert Sebra*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number6902
JournalNature Communications
Issue number1
StatePublished - Dec 2023


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