Bioengineering study finds two-cell mouse embryos already talking about their future

November 25, 2014

Bioengineers at the University of California, San Diego have discovered that mouse embryos are contemplating their cellular fates in the earliest stages after fertilization when the embryo has only two to four cells, a discovery that could upend the scientific consensus about when embryonic cells begin differentiating into cell types. Their research, which used single-cell RNA sequencing to look at every gene in the mouse genome, was published recently in the journal Genome Research. In addition, this group published a paper on analysis of "time-course"single-cell data which is taken at precise stages of embryonic development in the journal of Proceedings of the National Academy of Sciences.

"Until recently, we haven't had the technology to look at cells this closely," said Sheng Zhong, a bioengineering professor at UC San Diego Jacobs School of Engineering, who led the research. "Using single-cell RNA-sequencing, we were able to measure every gene in the mouse genome at multiple stages of development to find differences in gene expression at precise stages."

The findings reveal cellular activity that could provide insight into where normal developmental processes break down, leading to early miscarriages and birth defects.

The researchers discovered that a handful of genes are clearly signaling to each other at the two-cell and four-cell stage, which happens within days after an egg has been fertilized by sperm and before the embryo has implanted into the uterus. Among the identified genes are several genes belonging to the WNT signaling pathway, well-known for their role in cell-cell communications.

The prevailing view until now has been that mammalian embryos start differentiating into cell types after they have proliferated into large enough numbers to form subgroups. According to the co-authors Fernando Biase and Xiaoyi Cao, when the first cell fate decision is made is an open question. The first major task for an embryo is to decide which cells will begin forming the fetus, and which will form the placenta.

The research was funded by the National Institutes of Health (DP2OD007417) and the March of Dimes Foundation. The publications are "Cell fate inclination within 2-cell and 4-cell mouse embryos revealed by single-cell RNA sequencing", Genome Research, November 2014 and "Time-variant clustering model for understanding cell fate decisions", PNAS, November 2014.

Zhong's research in the field of systems or network biology applies engineering principals to understand how biological systems function. For example, they developed analytical methods to predict personal phenotypes, which refer to the physical description of an individual ranging from eye and hair color to health and disposition, using an individual's personal genome and epigenome. Epigenome refers to the chemical compounds in DNA that regulate gene expression and vary from person to person. Predicting phenotypes with genome and epigenome is an emerging area of research in the field of personalized medicine that scientists believe could provide new ways to predict and treat genetic disorders.
-end-


University of California - San Diego

Related Genome Articles from Brightsurf:

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Breakthrough in genome visualization
Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome.

Sturgeon genome sequenced
Sturgeons lived on earth already 300 million years ago and yet their external appearance seems to have undergone very little change.

A sea monster's genome
The giant squid is an elusive giant, but its secrets are about to be revealed.

Deciphering the walnut genome
New research could provide a major boost to the state's growing $1.6 billion walnut industry by making it easier to breed walnut trees better equipped to combat the soil-borne pathogens that now plague many of California's 4,800 growers.

Illuminating the genome
Development of a new molecular visualisation method, RNA-guided endonuclease -- in situ labelling (RGEN-ISL) for the CRISPR/Cas9-mediated labelling of genomic sequences in nuclei and chromosomes.

A genome under influence
References form the basis of our comprehension of the world: they enable us to measure the height of our children or the efficiency of a drug.

How a virus destabilizes the genome
New insights into how Kaposi's sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published Sept.

Better genome editing
Reich Group researchers develop a more efficient and precise method of in-cell genome editing.

Unlocking the genome
A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells.

Read More: Genome News and Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.