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Genetic dissection of intercellular interactions in vivo by membrane-permeable protein

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Unraveling cell–cell interaction is fundamental to understanding many biological processes. To date, genetic tools for labeling neighboring cells in mammals are not available. Here, we developed a labeling strategy based… Click to show full abstract

Unraveling cell–cell interaction is fundamental to understanding many biological processes. To date, genetic tools for labeling neighboring cells in mammals are not available. Here, we developed a labeling strategy based on the Cre-induced intercellular labeling protein (CILP). Cre-expressing donor cells release a lipid-soluble and membrane-permeable fluorescent protein that is then taken up by recipient cells, enabling fluorescent labeling of neighboring cells. Using CILP, we specifically labeled endothelial cells surrounding a special population of hepatocytes in adult mice and revealed their distinct gene signatures. Our results highlight the potential of CILP as a platform to reveal cell–cell interactions and communications in vivo.

Keywords: cell; membrane permeable; dissection intercellular; genetic dissection; protein

Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Year Published: 2022

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