Identification of an embryonic differentiation stage marked by Sox1 and FoxA2 co-expression using combined cell tracking and high dimensional protein imaging.

Autor: Arekatla G; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.; Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven - University of Leuven, Leuven, Belgium.; Laboratory of Neurobiology, VIB Center for Brain & Disease Research, Leuven, Belgium., Skylaki S; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Corredor Suarez D; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Jackson H; Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.; Institute of Molecular Health Sciences, ETH Zürich, Zürich, Switzerland.; Lunenfeld Tanenbaum Research Institute, Mount Sinai Health Systems; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada., Schapiro D; Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.; Institute of Molecular Health Sciences, ETH Zürich, Zürich, Switzerland.; Institute for Computational Biomedicine, Heidelberg University, Faculty of Medicine, Heidelberg University Hospital, Heidelberg, Germany.; Institute of Pathology, Heidelberg University Hospital, Heidelberg, Germany.; Translational Spatial Profiling Center (TSPC), Heidelberg, Germany., Engler S; Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland., Auler M; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Camargo Ortega G; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Hastreiter S; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Reimann A; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland., Loeffler D; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland.; Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA.; Department of Pathology and Laboratory Medicine, The University of Tennessee, Memphis, TN, USA., Bodenmiller B; Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.; Institute of Molecular Health Sciences, ETH Zürich, Zürich, Switzerland., Schroeder T; Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland. timm.schroeder@bsse.ethz.ch.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Sep 09; Vol. 15 (1), pp. 7860. Date of Electronic Publication: 2024 Sep 09.
DOI: 10.1038/s41467-024-52069-z
Abstrakt: Pluripotent mouse embryonic stem cells (ESCs) can differentiate to all germ layers and serve as an in vitro model of embryonic development. To better understand the differentiation paths traversed by ESCs committing to different lineages, we track individual differentiating ESCs by timelapse imaging followed by multiplexed high-dimensional Imaging Mass Cytometry (IMC) protein quantification. This links continuous live single-cell molecular NANOG and cellular dynamics quantification over 5-6 generations to protein expression of 37 different molecular regulators in the same single cells at the observation endpoints. Using this unique data set including kinship history and live lineage marker detection, we show that NANOG downregulation occurs generations prior to, but is not sufficient for neuroectoderm marker Sox1 upregulation. We identify a developmental cell type co-expressing both the canonical Sox1 neuroectoderm and FoxA2 endoderm markers in vitro and confirm the presence of such a population in the post-implantation embryo. RNASeq reveals cells co-expressing SOX1 and FOXA2 to have a unique cell state characterized by expression of both endoderm as well as neuroectoderm genes suggesting lineage potential towards both germ layers.
(© 2024. The Author(s).)
Databáze: MEDLINE
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