Anatomy and Neuroscience - Research Publications

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    Toward Guidelines for Research on Human Embryo Models Formed from Stem Cells
    Hyun, I ; Munsie, M ; Pera, MF ; Rivron, NC ; Rossant, J (CELL PRESS, 2020-02-11)
    Over the past few years, a number of research groups have reported striking progress on the generation of in vitro models from mouse and human stem cells that replicate aspects of early embryonic development. Not only do these models reproduce some key cell fate decisions but, especially in the mouse system, they also mimic the spatiotemporal arrangements of embryonic and extraembryonic tissues that are required for developmental patterning and implantation in the uterus. If such models could be developed for the early human embryo, they would have great potential benefits for understanding early human development, for biomedical science, and for reducing the use of animals and human embryos in research. However, guidelines for the ethical conduct of this line of work are at present not well defined. In this Forum article, we discuss some key aspects of this emerging area of research and provide some recommendations for its ethical oversight.
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    Cancer Stem Cells: Notes for Authors.
    Eaves, CJ ; Pera, MF (Elsevier BV, 2020-02-11)
    Stem Cell Reports frequently receives manuscripts dealing with the topic of cancer stem cells. Many of the submissions on this topic have major shortcomings in their content or limits to the conclusions that can be drawn from the results presented. The purpose of this Commentary is to highlight some of the underlying issues so that authors can enhance the strength of their research contributions.
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    Unique properties of a subset of human pluripotent stem cells with high capacity for self-renewal
    Lau, KX ; Mason, EA ; Kie, J ; De Souza, DP ; Kloehn, J ; Tull, D ; McConville, MJ ; Keniry, A ; Beck, T ; Blewitt, ME ; Ritchie, ME ; Naik, SH ; Zalcenstein, D ; Korn, O ; Su, S ; Romero, IG ; Spruce, C ; Baker, CL ; McGarr, TC ; Wells, CA ; Pera, MF (Nature Research, 2020-05-15)
    Archetypal human pluripotent stem cells (hPSC) are widely considered to be equivalent in developmental status to mouse epiblast stem cells, which correspond to pluripotent cells at a late post-implantation stage of embryogenesis. Heterogeneity within hPSC cultures complicates this interspecies comparison. Here we show that a subpopulation of archetypal hPSC enriched for high self-renewal capacity (ESR) has distinct properties relative to the bulk of the population, including a cell cycle with a very low G1 fraction and a metabolomic profile that reflects a combination of oxidative phosphorylation and glycolysis. ESR cells are pluripotent and capable of differentiation into primordial germ cell-like cells. Global DNA methylation levels in the ESR subpopulation are lower than those in mouse epiblast stem cells. Chromatin accessibility analysis revealed a unique set of open chromatin sites in ESR cells. RNA-seq at the subpopulation and single cell levels shows that, unlike mouse epiblast stem cells, the ESR subset of hPSC displays no lineage priming, and that it can be clearly distinguished from gastrulating and extraembryonic cell populations in the primate embryo. ESR hPSC correspond to an earlier stage of post-implantation development than mouse epiblast stem cells.