Genetic networks & Human Embryonic Stem Cells Behavior

At the initial stages of human embryonic development, a small group of cells called human embryonic stem cells (hESCs) manages growth and differentiation. Ultimately, giving rise to highly specialized human tissues. Human embryonic stem cells, as pluripotent cells, are of main interest to Regenerative and developmental biologist.

At Brigham and Women’s Hospital and Harvard Medical School, researchers by using genome-wide genetic screening to over-express and knock out large number of genes in hESCs. They discovered key networks that together controls pluripotency and prepare for cell death. Furthermore, it helps to certify optimal conditions for embryonic development. The findings offers new understanding for cancer genetics. It also provides a novel approach in research for regenerative medicine. “Elucidating how human embryonic stem cell function is control by genetics is essential for our understanding of developmental biology and regenerative medicine,” said Stephen Elledge. He is the professor of Genetics and Medicine at Brigham and HMS. “Our study provides the most extensive examination of gene functionality in hESCs to date.”

Affects of over and under expressing genes:

For the experiment, researchers overexpressed almost 12000 genes and knock out 18000 genes. While conducting the study, scientist observed a unique role played by hESC genes. So, after deleting these common genes including OCT4 and SOX2, stem cells unexpectedly increase their resistance to death. Thus, this showed that in normal conditions, pluripotency regulators also contribute to apoptosis pathways. Researchers believe that genetic link between pluripotency and cell death helps to check that if a stem cell is damage. If damaged, it is destroyed before it compromise the function of future cells and tissues.

These interrelated behaviors were evident in pluripotency regulator known as SAGA complex. The scientist showed that without the SAGA complex hESCs died less readily. Furthermore, its absences slow down the development of three germ layers (endoderm, mesoderm, and ectoderm). This proved that SAGA complex has main role in many activities of hESC. They found out that many genes that regulate the formation of germs layers also contribute to cancer growth when they are over or under expressed in somatic cells.


Besides offering a new approach on genetic basis of cancer, the study’s output genetic screening may help in future work in regenerative biology. “Genetic screens present a wonderful opportunity to probe how genetic networks contribute to interrelated cellular behaviors like growth, differentiation and survival,” said Naxerova. He is now an assistant professor in the Center for Systems Biology at Massachusetts General Hospital. “This approach can help regenerative and developmental biologists systematically map out genetic networks. These are helps in the formation of particular tissues and changes those genes to more efficiently grow different kinds of human tissues from stem cells.”