Single-Cell DNA-Methylation Analysis Reveals Epigenetic Chimerism in Preimplantation Embryos

Epigenetic alterations are increasingly recognized as causes of human cancers and disease. These aberrations are likely to arise during genomic reprogramming in mammalian preimplantation embryos, when their epigenomes are most vulnerable. However, this process is only partially understood because of...

Full description

Saved in:
Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2013-09, Vol.341 (6150), p.1110-1112
Main Authors: Lorthongpanich, Chanchao, Cheow, Lih Feng, Balu, Sathish, Quake, Stephen R., Knowles, Barbara B., Burkholder, William F., Solter, Davor, Messerschmidt, Daniel M.
Format: Article
Language:English
Subjects:
Animals
Blastocyst - metabolism
Blastomeres
Cells
Cellular Reprogramming - genetics
Chimerism
Defects
Diseases
DNA
DNA Methylation
Embryos
Epigenesis, Genetic
Epigenetics
Fatal
Gene Deletion
Gene Expression Regulation, Developmental
Genes
Genetic Loci
Humans
Loci
Maintenance
Methylation
Mice
Mice, Inbred C57BL
Mice, Transgenic
Nuclear Proteins - genetics
Oocytes
Pronucleus
Repressor Proteins - genetics
Single-Cell Analysis
Strategy
Transplants & implants
Tripartite Motif-Containing Protein 28
Viability
Zygotes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Epigenetic alterations are increasingly recognized as causes of human cancers and disease. These aberrations are likely to arise during genomic reprogramming in mammalian preimplantation embryos, when their epigenomes are most vulnerable. However, this process is only partially understood because of the experimental inaccessibility of early-stage embryos. Here, we introduce a methodologic advance, probing single cells for various DNA-methylation errors at multiple loci, to reveal failed maintenance of epigenetic mark results in chimeric mice, which display unpredictable phenotypes leading to developmental arrest. Yet we show that mouse pronuclear transfer can be used to ameliorate such reprogramming defects. This study not only details the epigenetic reprogramming dynamics in early mammalian embryos but also suggests diagnostic and potential future therapeutic applications.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1240617