Singapore scientists perform genome-wide study of human stem cells

Landmark identification of key human stem cell genes paves the way for future stem cell research

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SINGAPORE—A team of scientists from Singapore led by the Genome Institute of Singapore (GIS) and the Institute of Molecular and Cell Biology (IMCB)—two biomedical research institutes of Singapore's Agency of Science, Technology and Research (A*STAR)—have discovered what they believe are the most important genes in human embryonic stem cells (hESCs).

Reporting their findings this week in an early online version of Nature, they noted that they have used a genome-wide RNA interference screen to uncover genes involved in hESC pluripotency and self-renewal, and that this is a "crucial breakthrough" in discovering how human stem cells work.

Their research reportedly is the first-ever genome-wide study of human stem cells on such a massive scale, and the results of this work could have impact on treatment of a number of  debilitating conditions, including Parkinson's disease and traumatic spinal injury.

To conduct the work, Dr. Huck Hui Ng, GIS senior group leader for stem cell and development biology, and Dr. Frederic Bard, associate director for biology and IMCB principal investigator, combined the strengths of their teams to investigate the 21,000 genes in the entire human genome that regulate hESCs. Specifically, they focused on the regulation of two characteristic properties of hESCs: the capacity to turn into any type of cell in the human body (pluripotency), and the ability to retain that capacity indefinitely.

Out of the several key genes they identified, a particular gene known as PRDM14 was discovered to make it easier to turn a type of human cell (fibroblasts) into pluripotent stem cells.

The discoveries contribute to a fundamental understanding of the nature of stem cells and have implications for not just embryonic stem cells but also adult ones, the researchers note, and others agree. For example, Dr. Janet Rossant, a senior scientist in the Developmental & Stem Cell Biology Program at Toronto's The Hospital for Sick Children—who wasn't directly involved in the study—notes, "The unprecedented scale of this screen has added considerable new information to our understanding of pluripotency and will help efforts to improve reprogramming of adult cells."

In an interesting twist, the scientists found that PRDM14 played a key role in hESCs, but not in mouse ESCs, and the researchers say this significant new finding highlights the fundamental differences between stem cells from different species, and points to the continued need to use human cells in stem cell research.

"Very little is known about the molecular machines that drive stem cell states or the transcriptional profiles of hESCs," says GIS's Ng. "Our study helps to build a better understanding of hESCs and this will help in the development of technologies to further the utilities of these cells such as their potential to be used for clinical and therapeutic applications,. Dr. Bard's scientific expertise was invaluable in helping us crack another piece of the stem cell puzzle. I definitely look forward to collaborating with him on more projects that aim to peel away the mysteries surrounding stem cells."

"Huck Hui Ng and his colleagues continue to keep Singapore at the top table of countries plundering the secrets of human embryonic stem cell regulation," says Dr. Alan Colman, executive director of the Singapore Stem Cell Consortium. "This time they have deployed the first genome-wide functional screen to identify factors that maintain 'stemness' in these cells and yet again reveal major differences between mouse and human embryonic stem cells in the control of this important property."

Praising the reserachers' work in this area of stem cell research, professor Lee Eng Hin, executive director of the Biomedical Research Council for A*STAR, notes, "This is an examplar of a great cross institutional collaboration. The combined strength of stem cell and genomics experts has led to a great piece of world-class work. I hope to see more of such valuable partnerships in the future."

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