Abstract

Cell–cell communication and physical interactions play a vital role in cancer initiation, homeostasis, progression, and immune response. Here, we report a system that combines live capture of different cell types, co-incubation, time-lapse imaging, and gene expression profiling of doublets using a microfluidic integrated fluidic circuit that enables measurement of physical distances between cells and the associated transcriptional profiles due to cell–cell interactions. We track the temporal variations in natural killer—triple-negative breast cancer cell distances and compare them with terminal cellular transcriptome profiles. The results show the time-bound activities of regulatory modules and allude to the existence of transcriptional memory. Our experimental and bioinformatic approaches serve as a proof of concept for interrogating live-cell interactions at doublet resolution. Together, our findings highlight the use of our approach across different cancers and cell types.

A microfluidic system combines the capture, co-incubation, time-lapse imaging, and gene expression profiling of doublets to measure the distances between cells and associated transcriptional profiles due to cell–cell interactions.

Details

Title
Microfluidic live tracking and transcriptomics of cancer-immune cell doublets link intercellular proximity and gene regulation
Author
Flores, Bianca C. T. 1   VIAFID ORCID Logo  ; Chawla, Smriti 2 ; Ma, Ning 3 ; Sanada, Chad 4 ; Kujur, Praveen Kumar 5 ; Yeung, Rudy 6 ; Bellon, Margot B. 7   VIAFID ORCID Logo  ; Hukari, Kyle 8 ; Fowler, Brian 8 ; Lynch, Mark 9 ; Chinen, Ludmilla T. D. 10 ; Ramalingam, Naveen 8 ; Sengupta, Debarka 11   VIAFID ORCID Logo  ; Jeffrey, Stefanie S. 7   VIAFID ORCID Logo 

1  Stanford University School of Medicine, Department of Surgery, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); A.C.Camargo Cancer Center, Circulating Tumor Cells Group, São Paulo, Brazil (GRID:grid.413320.7) (ISNI:0000 0004 0437 1183); Portuguese Oncology Institute of Porto (IPO Porto), Cancer Biology and Epigenetics Group, IPO Porto Research Center (CI-IPOP), Porto, Portugal (GRID:grid.435544.7); Lillebaelt Hospital, Department of Clinical Genetics, Vejle, Denmark (GRID:grid.459623.f) (ISNI:0000 0004 0587 0347) 
2  Indraprastha Institute of Information Technology, Department of Computational Biology, New Delhi, India (GRID:grid.454294.a) (ISNI:0000 0004 1773 2689) 
3  Stanford University School of Medicine, Department of Surgery, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Akoya Biosciences, Menlo Park, USA (GRID:grid.509697.4) 
4  New Technologies Group, Fluidigm Corporation, South San Francisco, USA (GRID:grid.481625.c) (ISNI:0000 0004 0520 4061); Systems Integration Group, Inscripta Inc, Pleasanton, USA (GRID:grid.481625.c) 
5  Stanford University School of Medicine, Department of Surgery, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Jawaharlal Nehru University, Cancer Biology Laboratory, School of Life Sciences, New Delhi, India (GRID:grid.10706.30) (ISNI:0000 0004 0498 924X) 
6  New Technologies Group, Fluidigm Corporation, South San Francisco, USA (GRID:grid.481625.c) (ISNI:0000 0004 0520 4061); Seer Inc., Redwood City, USA (GRID:grid.481625.c) 
7  Stanford University School of Medicine, Department of Surgery, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956) 
8  New Technologies Group, Fluidigm Corporation, South San Francisco, USA (GRID:grid.481625.c) (ISNI:0000 0004 0520 4061) 
9  New Technologies Group, Fluidigm Corporation, South San Francisco, USA (GRID:grid.481625.c) (ISNI:0000 0004 0520 4061); BioSkryb Genomics, Inc., Durham, USA (GRID:grid.481625.c) 
10  A.C.Camargo Cancer Center, Circulating Tumor Cells Group, São Paulo, Brazil (GRID:grid.413320.7) (ISNI:0000 0004 0437 1183) 
11  Indraprastha Institute of Information Technology, Department of Computational Biology, New Delhi, India (GRID:grid.454294.a) (ISNI:0000 0004 1773 2689); Indraprastha Institute of Information Technology, Department of Computer Science and Engineering, New Delhi, India (GRID:grid.454294.a) (ISNI:0000 0004 1773 2689); Indraprastha Institute of Information Technology, Centre for Artificial Intelligence, New Delhi, India (GRID:grid.454294.a) (ISNI:0000 0004 1773 2689); Queensland University of Technology, Institute of Health and Biomedical Innovation, Brisbane, Australia (GRID:grid.1024.7) (ISNI:0000000089150953) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
23993642
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s42003-022-04205-y
ProQuest document ID
2735578852
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.