Systems based analysis of human embryos and gene networks involved in cell lineage allocation

Smith, H.L. et al. (2019) Systems based analysis of human embryos and gene networks involved in cell lineage allocation. BMC Genomics, 20, 171. (doi: 10.1186/s12864-019-5558-8) (PMID:30836937) (PMCID:PMC6399968)

Abstract

Background: Little is understood of the molecular mechanisms involved in the earliest cell fate decision in human development, leading to the establishment of the trophectoderm (TE) and inner cell mass (ICM) stem cell population. Notably, there is a lack of understanding of how transcriptional networks arise during reorganisation of the embryonic genome post-fertilisation. Results: We identified a hierarchical structure of preimplantation gene network modules around the time of embryonic genome activation (EGA). Using network models along with eukaryotic initiation factor (EIF) and epigenetic-associated gene expression we defined two sets of blastomeres that exhibited diverging tendencies towards ICM or TE. Analysis of the developmental networks demonstrated stage specific EIF expression and revealed that histone modifications may be an important epigenetic regulatory mechanism in preimplantation human embryos. Comparison to published RNAseq data confirmed that during EGA the individual 8-cell blastomeres are transcriptionally primed for the first lineage decision in development towards ICM or TE. Conclusions: Using multiple systems biology approaches to compare developmental stages in the early human embryo with single cell transcript data from blastomeres, we have shown that blastomeres considered to be totipotent are not transcriptionally equivalent. Furthermore we have linked the developmental interactome to individual blastomeres and to later cell lineage. This has clinical implications for understanding the impact of fertility treatments and developmental programming of long term health.

• Item Type: Articles
• Additional Information: The work presented here was conducted as part of two EU projects: FP7- HEALTH-2011-TWO-STAGE-278418, EPIHEALTH and FP7-PEOPLE-2012-ITN, PITN-GA-2012-317146, EPIHEALTHNET. In accordance with FP7, no new human embryos were used in this research. We also acknowledge funding from the Medical Research Council (MR/L004992/1), Central Manchester NHS Foundation Trust, the NIHR Manchester Clinical Research Facility and the University of Manchester.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sneddon, Dr Sharon
• Authors: Smith, H.L., Stevens, A., Minogue, B., Sneddon, S., Shaw, L., Wood, L., Adeniyi, T., Xiao, H., Lio, P., Kimber, S.J., and Brison, D.R.
• Subjects: Q Science > Q Science (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: BMC Genomics
• Publisher: BioMed Central
• ISSN: 1471-2164
• ISSN (Online): 1471-2164
• Copyright Holders: Copyright © 2019 The Authors
• First Published: First published in BMC Genomics 20: 171
• Publisher Policy: Reproduced under a Creative Commons License