Uncover the“black box” of developmental failure of implanting cloned embryos by 3D in vitro culture system
IMAGE: IN THE UPPER OF THE PICTURE, THE NORMAL EMBRYO GOES THROUGH A KEY MORPHOGENETIC STEP DURING THE TRANSITION FROM BLASTOCYST TO EGG CYLINDER THAT EPIBLAST CELLS MARKED BY RED ARE TRANSFORMED INTO A CUP-SHAPED EPITHELIUM. AT THE BOTTOM OF THE PICTURE, THE SCNT BLASTOCYST FAILS TO FORM PROPER EGG CYLINDER WITH A DISORGANIZED EPIBLAST STRUCTURE. view more
CREDIT: ©SCIENCE CHINA PRESS
Somatic cell nuclear transfer (SCNT), the currently unique reproductive engineering technique that produce new individuals from single differentiated somatic cell nuclei, has been successfully applied to clone more than 20 mammalian species, including cloned monkeys.The truth is, the broad usage of SCNT remains limited due to its low efficiency in generating live offspring, which mainly displays most cloned embryos dying during pre- and peri-implantation periods of gestation and abnormal placentas in full-term offspring.
Over the past decades, huge efforts have been made into understanding the reprogramming barriers and improving cloning efficiency during mammalian pre-implantation and post-implantation development.
However, during the peri-implantation stage, the implanting blastocysts invade the maternal uterine tissues and thus hidden from view. How do the morphogenetic and signaling events of SCNT happen during this stage? The developmental “black box” is previously difficult to study due to lack of proper culture systems.
Recently, a team from China led by Dr. Shaorong Gao have used an improved 3D in-vitro embryonic culture system to permit the visualization of the peri-implantation development of SCNT embryos and observed an abnormal morphogenetic step and pluripotency state in epiblast structure during the transition from blastocyst to egg cylinder. By conducting in-depth experiments and analysis, they characterized a new epigenetic mediated barriers-persistent Wnt signaling activity that can prevent the peri-implantation development of SCNT. Importantly, they presented a rescue approach that can attenuate the pluripotency transition and abnormal epigenetic remodeling and further improve cloning efficiency.
This study provides an important theoretical basis for understanding the development of peri-implantation embryos and will contribute to the expansion of the application of cloning technology in development biology, regenerative medicine and animal breeding industry.
See the article: Inhibition of Wnt activity improves peri-implantation development of somatic cell nuclear transfer embryos
JOURNAL
National Science Review
DOI
A schematic model showing the defective lineage specification reprogramming in SCNT embryos at the preimplantation stage. Persistent Wnt activity blocks the naïve-to-primed pluripotency transition of epiblast in peri-implantation cloned embryos, which accompanied by the aberrant H3K27me3 reprogramming. The barriers can result in the epiblast disorganization and implantation failure. Wnt manipulation can drive pluripotency transitions of epiblast cells to a considerable degree, further improving the peri-implantation development of cloned embryos.
CREDIT
©Science China Press
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