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Isoform-resolved transcriptome of the human preimplantation embryo

Author

Listed:
  • Denis Torre

    (Icahn School of Medicine at Mount Sinai)

  • Nancy J. Francoeur

    (Pacific Biosciences, Inc.)

  • Yael Kalma

    (Affiliated to Tel Aviv University)

  • Ilana Gross Carmel

    (Affiliated to Tel Aviv University)

  • Betsaida S. Melo

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Gintaras Deikus

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Kimaada Allette

    (Icahn School of Medicine at Mount Sinai)

  • Ron Flohr

    (Tel-Aviv University
    CORAL – Center Of Regeneration and Longevity, Tel-Aviv Sourasky Medical Center)

  • Maya Fridrikh

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Konstantinos Vlachos

    (Immunai Inc.)

  • Kent Madrid

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Hardik Shah

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Ying-Chih Wang

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Shwetha H. Sridhar

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Melissa L. Smith

    (University of Louisville)

  • Efrat Eliyahu

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Foad Azem

    (Affiliated to Tel Aviv University)

  • Hadar Amir

    (Affiliated to Tel Aviv University)

  • Yoav Mayshar

    (Weizmann Institute of Science)

  • Ivan Marazzi

    (University of California)

  • Ernesto Guccione

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Eric Schadt

    (Icahn School of Medicine at Mount Sinai)

  • Dalit Ben-Yosef

    (Affiliated to Tel Aviv University
    Tel-Aviv University
    CORAL – Center Of Regeneration and Longevity, Tel-Aviv Sourasky Medical Center)

  • Robert Sebra

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

Abstract

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.

Suggested Citation

  • 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, 2023. "Isoform-resolved transcriptome of the human preimplantation embryo," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42558-y
    DOI: 10.1038/s41467-023-42558-y
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