
@article {195,
	title = {Cell-type-specific signaling networks in heterocellular organoids},
	journal = {Nature Methods},
	volume = {17},
	year = {2020},
	pages = {335{\textendash}342},
	abstract = {<p>Despite the widespread adoption of organoids as biomimetic tissue models, methods to comprehensively analyze cell-type-specific post-translational modification (PTM) signaling networks in organoids are absent. Here, we report multivariate single-cell analysis of such networks in organoids and organoid cocultures. Simultaneous analysis by mass cytometry of 28 PTMs in \&gt;1 million single cells derived from small intestinal organoids reveals cell-type- and cell-state-specific signaling networks in stem, Paneth, enteroendocrine, tuft and goblet cells, as well as enterocytes. Integrating single-cell PTM analysis with thiol-reactive organoid barcoding in situ (TOBis) enables high-throughput comparison of signaling networks between organoid cultures. Cell-type-specific PTM analysis of colorectal cancer organoid cocultures reveals that shApc, KrasG12D and Trp53R172H cell-autonomously mimic signaling states normally induced by stromal fibroblasts and macrophages. These results demonstrate how standard mass cytometry workflows can be modified to perform high-throughput multivariate cell-type-specific signaling analysis of healthy and cancerous organoids.</p>},
	issn = {15487105},
	doi = {10.1038/s41592-020-0737-8},
	url = {http://dx.doi.org/10.1038/s41592-020-0737-8},
	author = {Qin, Xiao and Sufi, Jahangir and Vlckova, Petra and Kyriakidou, Pelagia and Acton, Sophie E. and Li, Vivian S.W. and Nitz, Mark and Tape, Christopher J.}
}
