Identification of an embryonic differentiation stage marked by Sox1 and FoxA2 co-expression using combined cell tracking and high dimensional protein imaging
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...
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| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
09 September 2024
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| In: |
Nature Communications
Year: 2024, Volume: 15, Pages: 1-16 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-024-52069-z |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-024-52069-z Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-024-52069-z 
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| Author Notes: | Geethika Arekatla, Stavroula Skylaki, David Corredor Suarez, Hartland Jackson, Denis Schapiro, Stefanie Engler, Markus Auler, German Camargo Ortega, Simon Hastreiter, Andreas Reimann, Dirk Loeffler, Bernd Bodenmiller, and Timm Schroeder |
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| 245 | 1 | 0 | |a Identification of an embryonic differentiation stage marked by Sox1 and FoxA2 co-expression using combined cell tracking and high dimensional protein imaging |c Geethika Arekatla, Stavroula Skylaki, David Corredor Suarez, Hartland Jackson, Denis Schapiro, Stefanie Engler, Markus Auler, German Camargo Ortega, Simon Hastreiter, Andreas Reimann, Dirk Loeffler, Bernd Bodenmiller, and Timm Schroeder |
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| 520 | |a 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. | ||
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