Genetic make-up of human and mouse embryos analyzed at unprecedented level using single-cell technique

By Shaun Mason | Jul 28, 2013 Research

UCLA scientists have used the powerful technology of single-cell RNA sequencing to track the genetic development of a human and a mouse embryo at an unprecedented level of accuracy. The success of this technique could lead to genetic diagnoses of diseases with higher resolution and in embryos earlier than ever achieved before, even when the embryo consists of only eight cells.

The study, published online ahead of press in the journal Nature,  was led by Guoping Fan, professor of human genetics and molecular biology and member of the Jonsson Comprehensive Cancer Center and the Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

“The advantages of this technique are twofold,” Fan said, “it is a much more comprehensive analysis than was achievable before and the technique requires a very minimal amount of sample material, just one cell.”

Besides having implications for genetic diagnoses, this technology may also have important uses in reproductive medicine, allowing detection in early embryos of diseases that derive from protein dysfunction, such as sickle cell disease, or for screening very early on for such genetic mutations as BRCA1 and BRCA2, which predispose women to breast and ovarian cancer.

“Previous to this paper we did not know this much about early human genetic development,” said study coauthor Kevin Huang, a post-doctoral scholar in Professor Fan’s laboratory, “now we can define what ‘normal’ looks like, so in the future we have a baseline to compare what ‘not normal’ looks like when looking for genetic problems. This is our first comprehensive glance at what is normal.”

With single-cell RNA sequencing, much more gene transcription was detected than before. “The question we asked,” Fan said, “is how does the gene network orchestrate driving pre-implantation early embryonic development from one cell to two cells, two cells to four cells, etc. We have uncovered that crucial gene network and we can now predict possible future genetic disorders at the 8-cell stage.”

This research was supported by the Chinese Ministry of Science and Technology, The International Science and Technology Cooperation Program of China, and the National Natural Science Foundation of China.

UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2013, the Jonsson Cancer Center was named among the top 12 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 14 consecutive years. For more information on the Jonsson Cancer Center, visit http://www.cancer.ucla.edu.

Genetics & Genomics Stem Cell Biology