Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

X marks the spot

08.11.2010
Cloning efficiency is undermined by widespread disruption of genomic regulation resulting largely from defective expression of a single gene

Despite their name, not all clones are created equal. This is especially true for the products of somatic cell nuclear transfer (SCNT), which entails the transplantation of the nucleus from a mature somatic cell, or non-reproductive cell, into an oocyte, or immature female ovum, whose nucleus has been removed.


Figure 1: The success rate of producing mice using SCNT cloning improves considerably after disrupting the Xist gene on the activated X chromosome of the donor nucleus. Copyright : © 2010 Atsuo Ogura

The result is a genomically reprogrammed cell that has been ‘tricked’ into acting like a fertilized egg, and subsequently develops into a clone of the nucleus-donor organism; however, the success rate for this procedure is remarkably low and many of the resulting clones exhibit a spectrum of developmental problems.

“We wanted to know if there were any clone-specific gene expression patterns in these embryos that might be related to their phenotypic abnormalities,” says Atsuo Ogura of the RIKEN BioResource Center in Tsukuba. To solve this mystery, Ogura and colleagues performed an extensive analysis of gene expression activity, comparing the profiles of SCNT-derived mouse embryos versus healthy embryos obtained from in vitro fertilization (IVF)1.

They observed a striking pattern of clone-specific reduced expression of genes situated on the X sex chromosome. This suggested that there may be a malfunction in the activity of the Xist locus, which ensures that gene expression levels in female cells mirror those of their single X chromosome-bearing male counterparts. “In female somatic cells, one of the X chromosomes is inactivated by RNA transcripts from the Xist gene on the same X chromosome,” explains Ogura. “In pre-implantation embryos, the choice of which X gets inactivated is derived from the ‘memory’ of oocytes and sperm.”

This memory appeared to be lost or disrupted in SCNT embryos, with many embryos showing evidence of widespread gene inactivation on both X chromosomes as early as the four-cell stage. However, the researchers found that this effect could be mitigated considerably by deriving SCNT embryos from donor nuclei in which the active X chromosome contains a defective copy of Xist. Strikingly, this also helped to normalize the expression of many non-X-linked genes that were abnormally regulated in SCNT but not IVF embryos, indicating that the effects of this X chromosome inactivation were more far-reaching than expected.

This strategy yielded eight- to nine-fold improvement in their SCNT success rate in mice (Fig. 1). Ogura and colleagues now hope to confirm that the same mechanism is specifically impeding cloning in other animal species as a prelude to the development of methods that might broadly bolster the efficacy of SCNT for both research and therapeutic applications.

The corresponding author for this highlight is based at the Bioresource Engineering Division, RIKEN BioResource Center

Journal information

Inoue, K., Kohda, T., Sugimoto, M., Sado, T., Ogonuki, N., Matoba, S., Shiura, H., Ikeda, R., Mochida, K., Fujii, T. et al. Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer. Science 330, 496–499 (2010).

gro-pr | Research asia research news
Further information:
http://www.riken.jp
http://www.researchsea.com

More articles from Life Sciences:

nachricht Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University

nachricht Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

Im Focus: Bacteria harness the lotus effect to protect themselves

Biofilms: Researchers find the causes of water-repelling properties

Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

Innovation 4.0: Shaping a humane fourth industrial revolution

17.05.2017 | Event News

 
Latest News

Scientists propose synestia, a new type of planetary object

23.05.2017 | Physics and Astronomy

Zap! Graphene is bad news for bacteria

23.05.2017 | Life Sciences

Medical gamma-ray camera is now palm-sized

23.05.2017 | Medical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>