An unsupervised method for physical cell interaction profiling of complex tissues

Autor: Nathanael, Andrews, Jason T, Serviss, Natalie, Geyer, Agneta B, Andersson, Ewa, Dzwonkowska, Iva, Šutevski, Rosan, Heijboer, Ninib, Baryawno, Marco, Gerling, Martin, Enge
Rok vydání: 2020
Předmět:
Zdroj: Nature methods. 18(8)
ISSN: 1548-7105
Popis: Cellular identity in complex multicellular organisms is determined in part by the physical organization of cells. However, large-scale investigation of the cellular interactome remains technically challenging. Here we develop cell interaction by multiplet sequencing (CIM-seq), an unsupervised and high-throughput method to analyze direct physical cell-cell interactions between cell types present in a tissue. CIM-seq is based on RNA sequencing of incompletely dissociated cells, followed by computational deconvolution into constituent cell types. CIM-seq estimates parameters such as number of cells and cell types in each multiplet directly from sequencing data, making it compatible with high-throughput droplet-based methods. When applied to gut epithelium or whole dissociated lung and spleen, CIM-seq correctly identifies known interactions, including those between different cell lineages and immune cells. In the colon, CIM-seq identifies a previously unrecognized goblet cell subtype expressing the wound-healing marker Plet1, which is directly adjacent to colonic stem cells. Our results demonstrate that CIM-seq is broadly applicable to unsupervised profiling of cell-type interactions in different tissue types.
Databáze: OpenAIRE