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

Autors de IIS La Fe

• Carlos Simon Valles

  Autor

• 

  Marcos Meseguer Escrivá

  Autor

Autors aliens a IIS La Fe

• Hernandez Mora, Jose Ramon
• Buhigas, Claudia
• Clark, Stephen
• Del Gallego Bonilla, Raquel
• Daskeviciute, Dagne
• Monteagudo-Sanchez, Ana
• Poo-Llanillo, Maria Eugenia
• Medrano, Jose Vicente
• Kelsey, Gavin
• Monk, David

Grups d'Investigació

• Biomarcadores, Medicina Genómica, Estadística y Análisis masivo de datos en Reproducción humana asistida

  

  Investigador Principal

  Marcos Meseguer Escrivá

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.

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Keywords

• CP: Stem cell research; DNA methylation; embryo arrest; embryonic genome activation; single cell; trophectoderm differentiation