Stem-cell consequences of embryo epigenetic defects.
BACKGROUND
The genetic code in the DNA of virtually every somatic cell can produce the entire complement of encoded proteins. Acetylation of histones and methylation of histones and DNA cytosine residues are part of the complex epigenetic regulatory process determining lineage-specific gene expression by altering the local structure of chromatin. After fertilisation, sperm DNA exchanges protamines for histones recruited from oocyte cytoplasm, reconfiguring both parental genomes into an epigenetic state conducive to activating the embryonic developmental programme. The identification of epigenetic reprogramming mechanisms is a major interest, rekindled by the ability of at least some somatic cells to acquire totipotency after somatic-cell nuclear transfer.


BACKGROUND
Recently, Woo SukHwang and colleagues (Science 2004; 303: 1669-74) derived a human embryonic stem-cell line from embryo therapeutic cloning. Chad Cowan and colleagues (N Engl JMed 2004; 350: 1353-56) produced 17 new lines from embryos supernumerary to infertility treatments. However, increasing evidence from a range of mammals shows a propensity for epigenetic errors with embryo technologies. If paralleled in human embryos, the effect on tumorigenic and differentiation properties of embryonic stem cells needs to be established. WHERE NEXT? Identifying the mechanisms in the oocyte that reprogramme a somatic cell to the embryonic state might allow somatic cells to be reprogrammed ex ovo by in-vitro manipulation of the epigenome. Because the oocyte is designed to reprogramme the sperm genome, which is in a different chromatin state from a somatic cell, perhaps many of the epigenetic errors induced by somatic-cell nuclear transfer could be avoided by a more targeted approach.
Allegrucci
Cinzia
C
Division of Obstetrics and Gynaecology, University of Nottingham, Queens Medical Centre, Nottingham NG7 2UH, UK.
Denning
Chris
C
Priddle
Helen
H
Young
Lorraine
L
D000818:Animals; D002460:Cell Line; D019976:Cloning, Organism; D019175:DNA Methylation; D004622:Embryo, Mammalian / Q000166:cytology*; D005314:Embryonic and Fetal Development; D044127:Epigenesis, Genetic; D018392:Genomic Imprinting; D006801:Humans; D033581:Stem Cell Transplantation / Q000009:adverse effects; D013234:Stem Cells / Q000502:physiology*