Isoform-resolved transcriptome of the human preimplantation embryo.

Autor: Torre D; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Francoeur NJ; Pacific Biosciences, Inc., Menlo Park, CA, 94025, USA., Kalma Y; Fertility and IVF Institute, Tel-Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Tel Aviv, 64239, Israel., Gross Carmel I; Fertility and IVF Institute, Tel-Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Tel Aviv, 64239, Israel., Melo BS; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Deikus G; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Allette K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Flohr R; Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, 69978, Israel.; CORAL - Center Of Regeneration and Longevity, Tel-Aviv Sourasky Medical Center, Tel Aviv, 64239, Israel., Fridrikh M; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Vlachos K; Immunai Inc., New York, NY, 10016, USA., Madrid K; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Shah H; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Wang YC; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Sridhar SH; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Smith ML; Department of Biochemistry and Molecular Genetics, University of Louisville, Louisville, KY, 40202, USA., Eliyahu E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Azem F; Fertility and IVF Institute, Tel-Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Tel Aviv, 64239, Israel., Amir H; Fertility and IVF Institute, Tel-Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Tel Aviv, 64239, Israel., Mayshar Y; Department of Molecular Cell Biology, Weizmann Institute of Science, 7610001, Rehovot, Israel., Marazzi I; Department of Biological Chemistry, Center for Epigenetics and Metabolism, University of California, Irvine, CA, 92697, USA., Guccione E; Center for OncoGenomics and Innovative Therapeutics (COGIT); Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Schadt E; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Ben-Yosef D; Fertility and IVF Institute, Tel-Aviv Sourasky Medical Center, Affiliated to Tel Aviv University, Tel Aviv, 64239, Israel. dalitb@tlvmc.gov.il.; Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv, 69978, Israel. dalitb@tlvmc.gov.il.; CORAL - Center Of Regeneration and Longevity, Tel-Aviv Sourasky Medical Center, Tel Aviv, 64239, Israel. dalitb@tlvmc.gov.il., Sebra R; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. robert.sebra@mssm.edu.; Center for Advanced Genomics Technology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. robert.sebra@mssm.edu.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. robert.sebra@mssm.edu.; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. robert.sebra@mssm.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Oct 30; Vol. 14 (1), pp. 6902. Date of Electronic Publication: 2023 Oct 30.
DOI: 10.1038/s41467-023-42558-y
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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