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
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).
Making fuel out of thick air
08.12.2017 | DOE/Argonne National Laboratory
‘Spying’ on the hidden geometry of complex networks through machine intelligence
08.12.2017 | Technische Universität Dresden
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
An interdisciplinary group of researchers interfaced individual bacteria with a computer to build a hybrid bio-digital circuit - Study published in Nature Communications
Scientists at the Institute of Science and Technology Austria (IST Austria) have managed to control the behavior of individual bacteria by connecting them to a...
Physicists in the Laboratory for Attosecond Physics (run jointly by LMU Munich and the Max Planck Institute for Quantum Optics) have developed an attosecond electron microscope that allows them to visualize the dispersion of light in time and space, and observe the motions of electrons in atoms.
The most basic of all physical interactions in nature is that between light and matter. This interaction takes place in attosecond times (i.e. billionths of a...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
11.12.2017 | Physics and Astronomy
11.12.2017 | Earth Sciences
11.12.2017 | Information Technology