Single-cell multi-omic analysis profiles defective genome activation and epigenetic reprogramming associated with human pre-implantation embryo arrest

Hernandez Mora, Jose Ramon, Buhigas, Claudia, Clark, Stephen, Del Gallego Bonilla, Raquel, Daskeviciute, Dagne, Monteagudo-Sánchez, Ana, Poo-Llanillo, Maria Eugenia, Medrano, Jose Vicente, Simón, Carlos, Meseguer, Marcos, Kelsey, Gavin and Monk, David (2023) Single-cell multi-omic analysis profiles defective genome activation and epigenetic reprogramming associated with human pre-implantation embryo arrest. Cell Reports, 42 (2). ISSN 2211-1247

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Abstract

During pre-implantation stages of mammalian development, maternally stored material promotes both the erasure of the sperm and oocyte epigenetic profiles and is responsible for concomitant genome activation. Here, we have utilized single-cell methylome and transcriptome sequencing (scM&T-seq) to quantify both mRNA expression and DNA methylation in oocytes and a developmental series of human embryos at single-cell resolution. We fully characterize embryonic genome activation and maternal transcript degradation and map key epigenetic reprogramming events in developmentally high-quality embryos. By comparing these signatures with early embryos that have undergone spontaneous cleavage-stage arrest, as determined by time-lapse imaging, we identify embryos that fail to appropriately activate their genomes or undergo epigenetic reprogramming. Our results indicate that a failure to successfully accomplish these essential milestones impedes the developmental potential of pre-implantation embryos and is likely to have important implications, similar to aneuploidy, for the success of assisted reproductive cycles.

Item Type:	Article
Faculty \ School:	Faculty of Science > School of Biological Sciences
UEA Research Groups:	Faculty of Science > Research Groups > Wheeler Group
Depositing User:	LivePure Connector
Date Deposited:	24 Feb 2023 15:30
Last Modified:	24 Feb 2023 15:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/91262
DOI:	10.1016/j.celrep.2023.112100

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