Self-organising stem cells

Human blastoids.jpg

    NEWS THREAD    

         3rd of June 2020         The National Academies of Sciences, Engineering, and Medicine of the U.S.A. published the proceedings of a workshop held in January 2020 in Washington and termed Examining the State of the Science of Mammalian Embryo Model Systems. The scientific and biomedical perspectives opened by stem cell-based embryo models are discussed, including for blastoids.

        3rd of March 2020       The lab of Janet Rossant (University of Toronto) and collaborators make detailed analysis of the single cell RNA sequencing data from blastoids, confirm the presence of analogs of the 3 founding cell types (Epi, Tr, PrE), and their transcriptional proximity to the cells of blastocysts. They also (and mainly) question the potential for extended/expanded potential stem cells to form functional trophoblasts.

  16th of December 2020     The lab of Madgalena Zernicka-Goetz (Caltech) makes use of our blastoid protocol. They confirm the presence of analogs of the 3 founding cell types (Epi, Tr, PrE), the potential to implant in utero, and then replace the embryonic stem cells by extended potential stem cells to investigate their capacity to form primitive endoderm. Great follow-up!

    8th of June 2021      The International Society for Stem Cell Research updated its ethical guidelines and included a framework for the use of human embryo models. A summary of the updates is published in Stem Cell Reports. The result of in-depth collegial discussions.

We research how self-organization contributes to 
coordinated cellular decision-making during development.

Fish schools, ant colonies, and bird flocks coordinate their collective behaviors to control the emergence and progression of patterns and functions. For example, fish schools adopt specific shapes that allow fishes to swim faster and protect themselves from predators better than individuals are able to. This broad range of decentralized, adaptive, and emergent behaviors based on local interactions and dynamic feedback is called self-organization. We explore how self-organization complements hierarchical intrinsic (e.g., HOX genes collinearity) and extrinsic (e.g., positional information) processes that shape the mammalian organism.

 

The blastocyst is the early mammalian organism before implantation (day 5 for mice, day 9 for humans). It is a powerful model because it is autonomous, adaptive, and small enough to be studied in great detail. We discovered how to promote the self-organization of stem cells into structures remarkably resembling the mouse and human blastocysts, and called these models blastoids (Nature 2018, Nature 2021). Blastoids are morphologically and transcriptionally similar to the blastocyst and contain analogs of all three cell types that further develop into the complete organism (embryonic and extra-embryonic tissues/organs). Because blastoids model the pre-implantation stage, they can be introduced into the uterus of a mouse (mouse model) or combined with uterine cells in vitro (human model) to recapitulate aspects of the hidden processes of implantation.

 

Contrary to blastocysts, blastoids are versatile in that they facilitate the more systematic modulation and analysis of the impact of cell numbers, states, and communication mechanisms on development. Blastoids are also amenable to screenings and complex genetic manipulations, which are at the base of scientific and biomedical discoveries. As such, they open previously inaccessible ways to investigate the interaction rules and design principles underlying embryonic development, but also to tackle global health problems of fertility decline, family planning, and of the developmental origin of health and diseases.

    NEWS THREAD    

       2nd of May 2018       We published our paper on mouse blastocyst-like structures formed solely from stem cells and called them blastoids. It is exciting for us to see a model of the full conceptus, which comprises analogs of the three founding lineages (epiblast, trophectoderm, primitive endoderm)! Because blastoids model a pre-implantation stage and form analogs of the trophectoderm that normally mediates the interaction with the uterus, we transferred them in utero, where they recapitulated aspects of implantation. However, no fetus or live mouse could form.

  16th of December 2019     The lab of Magdalena Zernicka-Goetz (Caltech) makes use of our blastoid protocol. They confirm the presence of analogs of the 3 founding cell types (Epi, Tr, PrE), the potential to implant in utero, and then replace the embryonic stem cells with extended potential stem cells (EPSCs) to investigate their capacity to form primitive endoderm. Great follow-up!

        3rd of March 2020       The lab of Janet Rossant (University of Toronto) and collaborators make a detailed analysis of the single-cell RNA sequencing data from mouse blastoids. They confirm the presence of analogs of the 3 founding cell types (Epi, Tr, PrE), and their transcriptional proximity to the cells of blastocysts. They also (and mainly) question the potential for extended/expanded potential stem cells (EPSCs) to form functional trophoblasts and propose that blastocyst-like structures formed with EPSCs-only form mesoderm-like cells rather than trophectoderm-like cells.

         3rd of June 2020         The National Academies of Sciences, Engineering, and Medicine of the U.S.A. published the proceedings of a workshop held in January 2020 in Washington and termed Examining the State of the Science of Mammalian Embryo Model Systems. The scientific and biomedical perspectives opened by stem cell-based embryo models are discussed, including for blastoids.

   1th of May 2021      The journal of the International Society for Stem Cell Research called Stem Cell Reports allowed Jianping Fu (University of Michigan) and I (Nicolas Rivron) to prepare a special edition on embryo models. This was an opportunity to gather experts in the field, summarise the state of the art, pinpoint the potential technical and ethical pitfalls, and think of the future. It will take a village to form embryo models! You can read an editorial that we wrote and download a Snapshot to decorate your lab fridge.

    8th of June 2021      The International Society for Stem Cell Research updated its ethical guidelines and included a framework for the use of human embryo models. This is the result of 2 years of in-depth and collegial discussions with scientists and ethicists worldwide. We also wrote a summary of the updates that was published in Stem Cell Reports.

    2nd of December 2021     We published our paper on human blastoids (Open access). They form with remarkable efficiency (>70%), recapitulate the temporal sequences of blastocyst development, and form cells transcriptionally similar to the blastocyst (>97% of the cells). Beyond these essential features, we observed that blastoids attach only to hormonally-primed endometrial cells, and do so via the polar trophectoderm as in utero, which increases the confidence in the functionality of the model. This model opens an avenue for mechanistic investigations of early human development. Kim Baumann from Nature Reviews Molecular Biology wrote a Research Highlight about it entitled A role model of human blastocysts, and Alok Javali from our lab wrote a story of this scientific journey entitled The making of... human blastoids. See also the summarising Tweet thread, by Alok Javali et al.

  26th of December 2021     The labs of Fredrik Lanner (Karolinska Institutet) and Sophie Petropoulos (Université de Montréal) led an independent consortium to benchmark the different 2021 attempts to form models of early human embryos. They included our model which, along with the one of the laboratories of Ge Guo / Austin Smith, formed cells that match well with the human blastocyst. Establishing reference maps including cells originating from pre-blastocyst and post-blastocyst conceptus is crucial to properly evaluate the generated cell types and stages. An appropriate state of the cells constituting the model (e.g., cell types, cell stage) is critical for blastoids to predict in vivo development. We commented on this Biorxiv paper as this open access preprint repository is wonderful not only for posting papers but also for discussing them. We hope our suggestions are helpful. See also the summarising Tweet thread by Alok Javali et al.

Affiliation

 

The laboratory is led by Nicolas Rivron at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna BioCenter (VBC), Vienna, Austria

Disclaimer

Content and statements offered on this website are not representative of statements, opinions, or policy of the IMBA institute, or the Austrian Academy of Science or the Vienna Biocenter. This website is not an official media outlet of the these institutions.

IMBA.png
OAW.png
VBC.png