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While it is already possible to obtain in vitro pluripotent cells (ie, cells capable of generating all tissues of an embryo) from any cell type, researchers from Maria-Elena Torres-Padilla’s team have pushed the limits of science even further. They managed to obtain totipotent cells with the same characteristics as those of the earliest embryonic stages and with even more interesting properties. Obtained in collaboration with Juanma Vaquerizas from the Max Planck Institute for Molecular Biomedicine (Münster, Germany), these results are published on 3rd of August in the journal Nature Structural & Molecular Biology.
Human embryonic stem cells have the potential to form in vitro neural tube -like structures of the embryo. ©Inserm/Benchoua Alexandra
For some years, it has been possible to re-programme differentiated cells into pluripotent ones, but not into totipotent cells. Now, the team of Maria-Elena Torres-Padilla has studied the characteristics of totipotent cells of the embryo and found factors capable of inducing a totipotent-like state.
When culturing pluripotent stem cells in vitro, a small amount of totipotent cells appear spontaneously; these are called “2C-like cells” (named after their resemblance to the 2-cell stage embryo). The researchers compared these cells to those present in early embryos in order to find their common characteristics and those that make them different from pluripotent cells. In particular, the teams found that the DNA was less condensed in totipotent cells and that the amount of the protein complex CAF1 was diminished. A closer look revealed that CAF1 -already known for its role in the assembly of chromatin (the organised state of DNA)- is responsible for maintaining the pluripotent state by ensuring that the DNA is wrapped around histones.
These results provide new elements for the understanding of pluripotency and could increase the efficiency of reprogramming somatic cells to be used for applications in regenerative medicine.
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Early embryonic-like cells are induced by down-regulation of replication-dependent chromatin assembly
Takashi Ishiuchi1, Rocio Enriquez-Gasca2, Eiji Mizutani3, Ana Bošković1, Celine Ziegler-Birling1, Diego Rodriguez-Terrones1, Teruhiko Wakayama3, Juan M. Vaquerizas2 & Maria-Elena Torres-Padilla1
1 Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U964, U de S, F-67404 ILLKIRCH, CU de Strasbourg, France.
2 Max Planck Institute for Molecular Biomedicine, 48149 Münster, Germany
3 Faculty of Life and Environmental Sciences, University of Yamanashi, 4-4-37 Takeda, Kofu, Yamanashi, Japan