mTOR activity paces human blastocyst stage developmental progression.
Dhanur P Iyer, Heidar Heidari Khoei, Vera A van der Weijden, Harunobu Kagawa, Saurabh J Pradhan, Maria Novatchkova, Afshan McCarthy, Teresa Rayon, Claire S Simon, Ilona Dunkel, Sissy E Wamaitha, Kay Elder, Phil Snell, Leila Christie, Edda G Schulz, Kathy K Niakan, Nicolas Rivron, Aydan Bulut-Karslioğlu
Author Information
Dhanur P Iyer: Stem Cell Chromatin Group, Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany; Institute of Chemistry and Biochemistry, Freie Universität Berlin, 14195 Berlin, Germany.
Heidar Heidari Khoei: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Vera A van der Weijden: Stem Cell Chromatin Group, Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Harunobu Kagawa: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Saurabh J Pradhan: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Maria Novatchkova: Institute of Molecular Pathology (IMP), Vienna BioCenter (VBC), 1030 Vienna, Austria.
Afshan McCarthy: The Human Embryo and Stem Cell Laboratory, Francis Crick Institute, London NW1 1AT, UK.
Teresa Rayon: Epigenetics & Signalling Programmes, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
Claire S Simon: The Human Embryo and Stem Cell Laboratory, Francis Crick Institute, London NW1 1AT, UK.
Ilona Dunkel: Systems Epigenetics, Otto-Warburg-Laboratories, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Sissy E Wamaitha: The Human Embryo and Stem Cell Laboratory, Francis Crick Institute, London NW1 1AT, UK.
Kay Elder: Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK.
Phil Snell: Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK.
Leila Christie: Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK.
Edda G Schulz: Systems Epigenetics, Otto-Warburg-Laboratories, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany.
Kathy K Niakan: The Human Embryo and Stem Cell Laboratory, Francis Crick Institute, London NW1 1AT, UK; Centre for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
Nicolas Rivron: Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), 1030 Vienna, Austria. Electronic address: nicolas.rivron@imba.oeaw.ac.at.
Aydan Bulut-Karslioğlu: Stem Cell Chromatin Group, Department of Genome Regulation, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany. Electronic address: aydan.karslioglu@molgen.mpg.de.
Many mammals can temporally uncouple conception from parturition by pacing down their development around the blastocyst stage. In mice, this dormant state is achieved by decreasing the activity of the growth-regulating mTOR signaling pathway. It is unknown whether this ability is conserved in mammals in general and in humans in particular. Here, we show that decreasing the activity of the mTOR signaling pathway induces human pluripotent stem cells (hPSCs) and blastoids to enter a dormant state with limited proliferation, developmental progression, and capacity to attach to endometrial cells. These in vitro assays show that, similar to other species, the ability to enter dormancy is active in human cells around the blastocyst stage and is reversible at both functional and molecular levels. The pacing of human blastocyst development has potential implications for reproductive therapies.
