Multiplexed single cell transcriptomics optimizes mesodermal patterning and hemogenic endothelial output from murine embryonic stem cells
Varnum-Finney, B.; Heck, A. M.; Srivatsan, S.; Dozono, S.; Wellington, R.; Nourigat-McKay, C.; Dignum, T.; Trapnell, C.; Hadland, B.
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Early patterning of mesodermal precursor populations is a key step of hematopoietic development in the embryo. To better understand this process, we employed sci-Plex, a high-throughput method of measuring multiplexed perturbations at the single-cell level, to evaluate the transcriptional response of mouse embryonic stem cells subjected to a gradient of two key morphogens in early mesoderm/hematopoietic development, Activin and BMP4. sci-Plex revealed varying combinations of Activin and BMP4 temporally influenced mesoderm patterning in vitro and subsequent production of cell types reflecting their in vivo counterparts. We leveraged sci-Plex data to further optimize the generation of intraembryonic-like hemogenic endothelial cells that serve as the precursors of hematopoietic lineages, including hematopoietic stem cells. This study highlights the utility of sci-Plex to dissect how dose and temporal integration of interacting signal pathways determines cell fates and serves as a resource to analyze cell fate choices in early mesoderm patterning at single cell resolution.
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