Embryonic stem cells can self-destruct when defective

Insight into genetic control of human embryonic stem cell fate has offered new insight into cancer genetics and could inform future work in regenerative medicine.

Scientists from Boston, Massachusetts carried out screening of key genetic networks controlling human embryonic stem cells growth and differentiation. They discovered a link between the genetic control of pluripotency and cell death in embryonic stems cells. This means that faulty embryonic stem cells have a built-in mechanism ensuring they self-destruct to avoid replication, which would affect the functioning of the developing embryo's future cells and tissues.

'Our methods allowed us to create an "atlas" of nearly every gene in the human genome and determine what its over-expression or loss does to the most fundamental first steps of human development.' Dr Kamila Naxerova, lead author of the study and principle investigator in the Centre for Systems Biology at Massachusetts General Hospital, Boston said. 'Instead of looking at genes one by one, we looked at thousands of genetic alterations at the same time to determine how they affect the proliferation of embryonic stem cells, and, subsequently, the development of the three germ layers that serve as the raw material for human tissues.'

Embryonic stem cells are pluripotent and give rise to all of the cell types that make up the body and control cell growth and differentiation at the earliest stages of human embryonic development. Researchers knocked out over 18,000 genes and overexpressed 12,000 genes in order to determine their role in early embryonic development. When the researchers deleted genes known to be involved in maintaining cell pluripotency in embryonic stem cells, they were surprised to find the cells were more likely to survive, indicating that under normal circumstances pluripotency regulators also control cell death, known as apoptosis.

Researchers also observed that many of the genes that regulate the formation of the three primary germ layers, the endoderm, mesoderm and ectoderm, are also known drivers of cancer growth when they are over- or under-expressed in somatic cells.

'Elucidating how human embryonic stem cell function is controlled by genetics is essential for our understanding of developmental biology and regenerative medicine,' said co-corresponding author Professor Stephen Elledge, professor of genetics and medicine at the Brigham and Harvard Medical School. 'Our study provides the most extensive examination of gene functionality in [human embryonic stem cells] to date.'

Previous research has shown that human embryonic cells that display aneuploidy, where the cell has the wrong number of chromosomes, are removed from the part of the embryo that becomes the fetus and instead make up the part of the embryo that becomes the placenta (see BioNews 1097).